Variant 17-41097654-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031960.3(KRTAP4-8):c.431G>C(p.Cys144Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000258 in 151,192 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: 𝑓 0.00026 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00063 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP4-8
NM_031960.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0850

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14781702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRTAP4-8	NM_031960.3 linkuse as main transcript	c.431G>C	p.Cys144Ser	missense_variant	1/1	ENST00000333822.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRTAP4-8	ENST00000333822.5 linkuse as main transcript	c.431G>C	p.Cys144Ser	missense_variant	1/1		NM_031960.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000258

AC:

AN:

151192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000471

Gnomad OTH

AF:

0.000964

GnomAD3 exomes

AF:

0.000384

AC:

AN:

200594

Hom.:

AF XY:

0.000369

AC XY:

AN XY:

108380

show subpopulations

Gnomad AFR exome

AF:

0.000201

Gnomad AMR exome

AF:

0.0000705

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000365

Gnomad FIN exome

AF:

0.000262

Gnomad NFE exome

AF:

0.000740

Gnomad OTH exome

AF:

0.000573

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000631

AC:

908

AN:

1438514

Hom.:

Cov.:

AF XY:

0.000603

AC XY:

430

AN XY:

713448

show subpopulations

Gnomad4 AFR exome

AF:

0.0000615

Gnomad4 AMR exome

AF:

0.000173

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.000308

Gnomad4 NFE exome

AF:

0.000767

Gnomad4 OTH exome

AF:

0.000453

GnomAD4 genome

AF:

0.000258

AC:

AN:

151192

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

AN XY:

73784

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000190

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.000964

Alfa

AF:

0.000434

Hom.:

Bravo

AF:

0.000385

ExAC

AF:

0.000433

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

Jun 01, 2023

The c.431G>C (p.C144S) alteration is located in exon 1 (coding exon 1) of the KRTAP4-8 gene. This alteration results from a G to C substitution at nucleotide position 431, causing the cysteine (C) at amino acid position 144 to be replaced by a serine (S). 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

0.19

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.086

T;.

Eigen

Uncertain

0.33

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.5

M;.

MutationTaster

Benign

0.62

PrimateAI

Benign

0.25

PROVEAN

Pathogenic

-8.3

D;.

REVEL

Benign

0.14

Sift

Benign

0.054

T;.

Sift4G

Uncertain

0.033

D;D

Polyphen

1.0

D;.

Vest4

0.24

MutPred

0.63

Gain of relative solvent accessibility (P = 0.005);.;

MVP

0.15

MPC

0.11

ClinPred

0.36

GERP RS

3.7

Varity_R

0.45

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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