Variant 6-39540023-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_145027.6(KIF6):c.1625G>T(p.Ser542Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KIF6
NM_145027.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.361

Variant links:

Genes affected

KIF6 (HGNC:21202): (kinesin family member 6) This gene encodes a member of a family of molecular motors which are involved in intracellular transport of protein complexes, membrane organelles, and messenger ribonucleic acid along microtubules. Kinesins function as homodimeric molecules with two N-terminal head domains that move along microtubules and two C-terminal tail domains that interact with the transported cargo, either directly or indirectly, through adapter molecules. This gene is ubiquitously expressed in coronary arteries and other vascular tissue. A naturally occurring mutation in this gene is associated with coronary heart disease. [provided by RefSeq, May 2017]

KIF6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26522136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF6	NM_145027.6 link	c.1625G>T	p.Ser542Ile	missense_variant	13/23	ENST00000287152.12	NP_659464.3	Q6ZMV9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KIF6	ENST00000287152.12 link	c.1625G>T	p.Ser542Ile	missense_variant	13/23	2	NM_145027.6	ENSP00000287152.7	Q6ZMV9-1
KIF6	ENST00000458470.5 link	c.1298G>T	p.Ser433Ile	missense_variant	10/19	1		ENSP00000409417.1	H0Y718
KIF6	ENST00000538893.5 link	c.-3+4481G>T		intron_variant		5		ENSP00000441435.2	F6VGH2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000411

AC:

AN:

243594

Hom.:

AF XY:

0.00000761

AC XY:

AN XY:

131492

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000306

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:

6.88e-7

AC:

AN:

1453946

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722790

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000234

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 02, 2024

The c.1625G>T (p.S542I) alteration is located in exon 13 (coding exon 13) of the KIF6 gene. This alteration results from a G to T substitution at nucleotide position 1625, causing the serine (S) at amino acid position 542 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0077

Eigen

Benign

-0.0034

Eigen_PC

Benign

0.026

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.70

M_CAP

Benign

0.052

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.6

REVEL

Benign

0.14

Sift

Benign

0.041

Sift4G

Benign

0.33

Polyphen

0.80

Vest4

0.36

MutPred

0.38

Loss of phosphorylation at S542 (P = 0.0169);

MVP

0.80

MPC

0.10

ClinPred

0.30

GERP RS

4.2

Varity_R

0.15

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over