NM_198525.3:c.1159C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198525.3(KIF7):​c.1159C>T​(p.Arg387Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R387S) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000036 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

KIF7
NM_198525.3 missense

Scores

2
11
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.65
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIF7NM_198525.3 linkc.1159C>T p.Arg387Cys missense_variant Exon 5 of 19 ENST00000394412.8 NP_940927.2 Q2M1P5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIF7ENST00000394412.8 linkc.1159C>T p.Arg387Cys missense_variant Exon 5 of 19 5 NM_198525.3 ENSP00000377934.3 Q2M1P5
KIF7ENST00000445906.1 linkn.*818C>T non_coding_transcript_exon_variant Exon 5 of 5 1 ENSP00000395906.1 F8WD21
KIF7ENST00000445906.1 linkn.*818C>T 3_prime_UTR_variant Exon 5 of 5 1 ENSP00000395906.1 F8WD21
KIF7ENST00000696512.1 linkc.1282C>T p.Arg428Cys missense_variant Exon 5 of 19 ENSP00000512678.1 A0A8Q3SIQ8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000357
AC:
4
AN:
1119716
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
AN XY:
544350
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000428
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Uncertain
0.029
T
BayesDel_noAF
Benign
-0.20
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.47
T
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.76
T
M_CAP
Pathogenic
0.93
D
MetaRNN
Uncertain
0.54
D
MetaSVM
Benign
-0.31
T
MutationAssessor
Benign
0.90
L
PrimateAI
Pathogenic
0.96
D
PROVEAN
Uncertain
-2.9
D
REVEL
Benign
0.26
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.024
D
Polyphen
0.99
D
Vest4
0.32
MutPred
0.24
Loss of MoRF binding (P = 0.0731);
MVP
0.81
MPC
0.16
ClinPred
0.93
D
GERP RS
3.5
Varity_R
0.30
gMVP
0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-90191770; API