rs150248985

Variant names:

• chr15-89628507-G-A
• rs150248985
• NM_198525.3:c.3944C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-89628507-G-A
• chr15-89628507-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_198525.3(KIF7):​c.3944C>T​(p.Pro1315Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,613,006 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1315R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (5 hom.)
• Consequence: KIF7 NM_198525.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:9
• Conservation: PhyloP100: 2.85
• Publications: 8 publications found

Genes affected

KIF7 (HGNC:30497): (kinesin family member 7) This gene encodes a cilia-associated protein belonging to the kinesin family. This protein plays a role in the sonic hedgehog (SHH) signaling pathway through the regulation of GLI transcription factors. It functions as a negative regulator of the SHH pathway by preventing inappropriate activation of GLI2 in the absence of ligand, and as a positive regulator by preventing the processing of GLI3 into its repressor form. Mutations in this gene have been associated with various ciliopathies. [provided by RefSeq, Oct 2011]

TICRR (HGNC:28704): (TOPBP1 interacting checkpoint and replication regulator) Enables chromatin binding activity. Involved in regulation of DNA-dependent DNA replication initiation. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0071223974).
• BP6: Variant 15-89628507-G-A is Benign according to our data. Variant chr15-89628507-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 195000.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00132 (201/152314) while in subpopulation NFE AF = 0.0015 (102/68014). AF 95% confidence interval is 0.00126. There are 0 homozygotes in GnomAd4. There are 104 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198525.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF7	NM_198525.3	MANE Select	c.3944C>T	p.Pro1315Leu	missense	Exon 19 of 19	NP_940927.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF7	ENST00000394412.8	TSL:5 MANE Select	c.3944C>T	p.Pro1315Leu	missense	Exon 19 of 19	ENSP00000377934.3
	TICRR	ENST00000561095.1	TSL:1	n.*97-923G>A		intron	N/A	ENSP00000453922.1
	KIF7	ENST00000696512.1		c.4067C>T	p.Pro1356Leu	missense	Exon 19 of 19	ENSP00000512678.1

Frequencies

GnomAD3 genomes AF: 0.00132 AC: 201 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00301

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00159 AC: 395 AN: 248418 AF XY: 0.00153

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00953

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00204

Gnomad NFE exome AF: 0.00152

Gnomad OTH exome AF: 0.00263

GnomAD4 exome AF: 0.00137 AC: 2005 AN: 1460692 Hom.: 5 Cov.: 31 AF XY: 0.00142 AC XY: 1034 AN XY: 726656

African (AFR) AF: 0.0000896 AC: 3 AN: 33476

American (AMR) AF: 0.00141 AC: 63 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0100 AC: 261 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000591 AC: 51 AN: 86232

European-Finnish (FIN) AF: 0.00261 AC: 137 AN: 52414

Middle Eastern (MID) AF: 0.0132 AC: 76 AN: 5768

European-Non Finnish (NFE) AF: 0.00118 AC: 1316 AN: 1111904

Other (OTH) AF: 0.00162 AC: 98 AN: 60382

GnomAD4 genome AF: 0.00132 AC: 201 AN: 152314 Hom.: 0 Cov.: 32 AF XY: 0.00140 AC XY: 104 AN XY: 74476

African (AFR) AF: 0.000192 AC: 8 AN: 41564

American (AMR) AF: 0.000653 AC: 10 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00301 AC: 32 AN: 10628

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00150 AC: 102 AN: 68014

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00169 Hom.: 4

Bravo AF: 0.00122

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00221 AC: 19

ExAC AF: 0.00149 AC: 181

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00125

EpiControl AF: 0.00202

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:9

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:5

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Feb 18, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KIF7: BS2

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Acrocallosal syndrome Uncertain:1 Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

not specified Benign:1

Apr 18, 2017

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Inborn genetic diseases Benign:1

Jul 22, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

KIF7-related disorder Benign:1

Mar 21, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.77
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.037
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.0071	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.8
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.11
Sift	Benign	0.47	T
Sift4G	Benign	0.38	T
Polyphen		0.18	B
Vest4		0.091
MVP		0.48
MPC		0.027
ClinPred		0.034	T
GERP RS		5.3
Varity_R		0.086
gMVP		0.19
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs150248985; hg19: chr15-90171738; COSMIC: COSV51538895; COSMIC: COSV51538895;