Variant 17-41097588-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031960.3(KRTAP4-8):c.497G>A(p.Arg166His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000625 in 1,569,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

KRTAP4-8
NM_031960.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.394

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07224709).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRTAP4-8	NM_031960.3 linkuse as main transcript	c.497G>A	p.Arg166His	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.497G>A	p.Arg166His	missense_variant	1/1		NM_031960.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000126

AC:

AN:

151382

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000735

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000657

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000165

AC:

AN:

181520

Hom.:

AF XY:

0.000176

AC XY:

AN XY:

96536

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.000117

Gnomad EAS exome

AF:

0.00109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000532

Gnomad OTH exome

AF:

0.000613

GnomAD4 exome

AF:

0.0000557

AC:

AN:

1417650

Hom.:

Cov.:

AF XY:

0.0000571

AC XY:

AN XY:

700902

show subpopulations

Gnomad4 AFR exome

AF:

0.0000315

Gnomad4 AMR exome

AF:

0.000235

Gnomad4 ASJ exome

AF:

0.000119

Gnomad4 EAS exome

AF:

0.00114

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000129

Gnomad4 OTH exome

AF:

0.000136

GnomAD4 genome

AF:

0.000125

AC:

AN:

151498

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74050

show subpopulations

Gnomad4 AFR

AF:

0.0000732

Gnomad4 AMR

AF:

0.000656

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000774

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000245

Hom.:

Bravo

AF:

0.000178

ExAC

AF:

0.0000342

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

Apr 12, 2024

The c.497G>A (p.R166H) alteration is located in exon 1 (coding exon 1) of the KRTAP4-8 gene. This alteration results from a G to A substitution at nucleotide position 497, causing the arginine (R) at amino acid position 166 to be replaced by a histidine (H). 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

0.15

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.066

T;.

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.038

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.13

T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

0.99

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-3.8

D;.

REVEL

Benign

0.12

Sift

Benign

0.056

T;.

Sift4G

Benign

0.12

T;T

Polyphen

0.99

D;.

Vest4

0.14

MutPred

0.40

Gain of glycosylation at T163 (P = 0.0615);.;

MVP

0.081

MPC

0.11

ClinPred

0.14

GERP RS

1.5

Varity_R

0.10

gMVP

0.084

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