Variant 17-41097545-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_031960.3(KRTAP4-8):c.540C>G(p.Cys180Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,410,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.000016 ( 0 hom. )

Consequence

KRTAP4-8
NM_031960.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.225

Variant links:

Genes affected

KRTAP4-8 (HGNC:17230): (keratin associated protein 4-8) Involved in aging and hair cycle. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP4-8 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=0.4003203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP4-8	NM_031960.3 linkuse as main transcript	c.540C>G	p.Cys180Trp	missense_variant	1/1	ENST00000333822.5	NP_114166.1	Q9BYQ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP4-8	ENST00000333822.5 linkuse as main transcript	c.540C>G	p.Cys180Trp	missense_variant	1/1	6	NM_031960.3	ENSP00000328444.4		Q9BYQ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000572

AC:

AN:

174898

Hom.:

AF XY:

0.0000108

AC XY:

AN XY:

92452

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000208

GnomAD4 exome

AF:

0.0000156

AC:

AN:

1410002

Hom.:

Cov.:

AF XY:

0.0000172

AC XY:

AN XY:

697154

show subpopulations

Gnomad4 AFR exome

AF:

0.0000719

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:

0.0000175

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000859

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

May 15, 2024

The c.540C>G (p.C180W) alteration is located in exon 1 (coding exon 1) of the KRTAP4-8 gene. This alteration results from a C to G substitution at nucleotide position 540, causing the cysteine (C) at amino acid position 180 to be replaced by a tryptophan (W). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.25

DANN

Benign

0.93

DEOGEN2

Benign

0.30

T;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.061

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

M;.

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-8.7

D;.

REVEL

Benign

0.094

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.54

MutPred

0.52

Gain of loop (P = 0.069);.;

MVP

0.048

MPC

0.12

ClinPred

0.39

GERP RS

-2.4

Varity_R

0.41

gMVP

0.18

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.

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