rs8179065

Positions:

• chr15-89652777-C-A
• chr15-89652777-C-T

Variant summary

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

The NM_198525.3(KIF7):​c.154G>T​(p.Asp52Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. D52N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KIF7 NM_198525.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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]

ACMG classification

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/exons	MANE	Protein	UniProt
KIF7	NM_198525.3	c.154G>T	p.Asp52Tyr	missense_variant	2/19	ENST00000394412.8	NP_940927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF7	ENST00000394412.8	c.154G>T	p.Asp52Tyr	missense_variant	2/19	5	NM_198525.3	ENSP00000377934	P2
KIF7	ENST00000445906.1	c.154G>T	p.Asp52Tyr	missense_variant, NMD_transcript_variant	2/5	1		ENSP00000395906
KIF7	ENST00000696512.1	c.277G>T	p.Asp93Tyr	missense_variant	2/19			ENSP00000512678	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.81	D
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.047
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-7.9	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.50
MutPred		0.47		Gain of MoRF binding (P = 0.0723);
MVP		0.82
MPC		0.14
ClinPred		0.99	D
GERP RS		2.4
Varity_R		0.79
gMVP		0.65

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

Other links and lift over

dbSNP: rs8179065; hg19: chr15-90196008;