rs587780374

Variant names:

• chr15-89648539-G-T
• rs587780374
• NM_198525.3:c.1159C>A
• KIF7 p.Arg387Ser

Your query was ambiguous. Multiple possible variants found:

• chr15-89648539-G-T
• chr15-89648539-G-A
• chr15-89648539-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_198525.3(KIF7):​c.1159C>A​(p.Arg387Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000893 in 1,119,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. R387R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.9e-7 (0 hom.)
• Consequence: KIF7 NM_198525.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.65
• Publications: 0 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]

KIF7 Gene-Disease associations (from GenCC):

• acrocallosal syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• hydrolethalus syndrome 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• hydrolethalus syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• multiple epiphyseal dysplasia, Al-Gazali type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• orofaciodigital syndrome type 6

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24779537).
• BP6: Variant 15-89648539-G-T is Benign according to our data. Variant chr15-89648539-G-T is described in ClinVar as Benign. ClinVar VariationId is 129403.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF7	NM_198525.3	MANE Select	c.1159C>A	p.Arg387Ser	missense	Exon 5 of 19	NP_940927.2	Q2M1P5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF7	ENST00000394412.8	TSL:5 MANE Select	c.1159C>A	p.Arg387Ser	missense	Exon 5 of 19	ENSP00000377934.3	Q2M1P5
	KIF7	ENST00000445906.1	TSL:1	n.*818C>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000395906.1	F8WD21
	KIF7	ENST00000445906.1	TSL:1	n.*818C>A		3_prime_UTR	Exon 5 of 5	ENSP00000395906.1	F8WD21

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000396 AC: 1 AN: 25258 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000337

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 8.93e-7 AC: 1 AN: 1119716 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 544350

African (AFR) AF: 0.00 AC: 0 AN: 20362

American (AMR) AF: 0.000103 AC: 1 AN: 9666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13886

East Asian (EAS) AF: 0.00 AC: 0 AN: 20284

South Asian (SAS) AF: 0.00 AC: 0 AN: 48298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3332

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 934940

Other (OTH) AF: 0.00 AC: 0 AN: 42936

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.096
Eigen_PC	Benign	-0.016
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.59	T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.7
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.15
Sift	Benign	0.038	D
Sift4G	Benign	0.32	T
Varity_R		0.38
gMVP		0.54
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs587780374;

hg19: chr15-90191770;