Genetic Variant KIF7:p.Gly388Gly (chr15-89648534-G-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_198525.3(KIF7):c.1164C>G(p.Gly388Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000937 in 1,066,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G388G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 9.4e-7 ( 0 hom. )

Consequence

KIF7
NM_198525.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.271

Publications

0 publications found

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]

KIF7 Gene-Disease associations (from GenCC):

acrocallosal syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
neurodevelopmental disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
hydrolethalus syndrome 2
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
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

KIF7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP7

Synonymous conserved (PhyloP=0.271 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF7	NM_198525.3 link	c.1164C>G	p.Gly388Gly	synonymous_variant	Exon 5 of 19	ENST00000394412.8	NP_940927.2	Q2M1P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIF7	ENST00000394412.8 link	c.1164C>G	p.Gly388Gly	synonymous_variant	Exon 5 of 19	5	NM_198525.3	ENSP00000377934.3	Q2M1P5
KIF7	ENST00000445906.1 link	n.*823C>G		non_coding_transcript_exon_variant	Exon 5 of 5	1		ENSP00000395906.1	F8WD21
KIF7	ENST00000445906.1 link	n.*823C>G		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000395906.1	F8WD21
KIF7	ENST00000696512.1 link	c.1287C>G	p.Gly429Gly	synonymous_variant	Exon 5 of 19			ENSP00000512678.1	A0A8Q3SIQ8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.37e-7

AC:

AN:

1066864

Hom.:

Cov.:

AF XY:

0.00000194

AC XY:

AN XY:

514772

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19370

American (AMR)

AF:

0.00

AC:

AN:

7170

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11634

East Asian (EAS)

AF:

0.00

AC:

AN:

17716

South Asian (SAS)

AF:

0.00

AC:

AN:

40840

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22984

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2888

European-Non Finnish (NFE)

AF:

0.00000111

AC:

AN:

904128

Other (OTH)

AF:

0.00

AC:

AN:

40134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.0

(source)

DANN

Benign

0.75

PhyloP100

0.27

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over