rs975756878

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The NM_198525.3(KIF7):​c.1164C>T​(p.Gly388Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000906 in 1,214,262 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

KIF7
NM_198525.3 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 0.271
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 15-89648534-G-A is Benign according to our data. Variant chr15-89648534-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 582482.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=0.271 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KIF7NM_198525.3 linkuse as main transcriptc.1164C>T p.Gly388Gly synonymous_variant 5/19 ENST00000394412.8 NP_940927.2 Q2M1P5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KIF7ENST00000394412.8 linkuse as main transcriptc.1164C>T p.Gly388Gly synonymous_variant 5/195 NM_198525.3 ENSP00000377934.3 Q2M1P5
KIF7ENST00000445906.1 linkuse as main transcriptn.*823C>T non_coding_transcript_exon_variant 5/51 ENSP00000395906.1 F8WD21
KIF7ENST00000445906.1 linkuse as main transcriptn.*823C>T 3_prime_UTR_variant 5/51 ENSP00000395906.1 F8WD21
KIF7ENST00000696512.1 linkuse as main transcriptc.1287C>T p.Gly429Gly synonymous_variant 5/19 ENSP00000512678.1 A0A8Q3SIQ8

Frequencies

GnomAD3 genomes
AF:
0.0000339
AC:
5
AN:
147398
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000337
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000776
AC:
1
AN:
12894
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
8146
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000678
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.00000562
AC:
6
AN:
1066864
Hom.:
0
Cov.:
27
AF XY:
0.00000389
AC XY:
2
AN XY:
514772
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000418
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000111
Gnomad4 OTH exome
AF:
0.0000498
GnomAD4 genome
AF:
0.0000339
AC:
5
AN:
147398
Hom.:
0
Cov.:
32
AF XY:
0.0000418
AC XY:
3
AN XY:
71748
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000337
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000907

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitterclinical testingRevvity Omics, RevvityMay 03, 2021- -
Likely benign, criteria provided, single submitterclinical testingGeneDxAug 12, 2019- -
KIF7-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJan 05, 2021This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Acrocallosal syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 04, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
6.2
DANN
Benign
0.96

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs975756878; hg19: chr15-90191765; API