Variant 17-41097858-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_031960.3(KRTAP4-8):c.227A>G(p.Lys76Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00096 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000095 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP4-8
NM_031960.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.66

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0141225755).

BP6

Variant 17-41097858-T-C is Benign according to our data. Variant chr17-41097858-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2286835.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRTAP4-8	NM_031960.3 linkuse as main transcript	c.227A>G	p.Lys76Arg	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.227A>G	p.Lys76Arg	missense_variant	1/1		NM_031960.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000934

AC:

AN:

38524

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00136

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000497

Gnomad ASJ

AF:

0.00118

Gnomad EAS

AF:

0.000932

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00228

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000777

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000954

AC:

115

AN:

1205730

Hom.:

Cov.:

162

AF XY:

0.000114

AC XY:

AN XY:

594650

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000413

Gnomad4 ASJ exome

AF:

0.000109

Gnomad4 EAS exome

AF:

0.0000364

Gnomad4 SAS exome

AF:

0.000458

Gnomad4 FIN exome

AF:

0.000149

Gnomad4 NFE exome

AF:

0.0000605

Gnomad4 OTH exome

AF:

0.000175

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000959

AC:

AN:

38584

Hom.:

Cov.:

AF XY:

0.000985

AC XY:

AN XY:

19284

show subpopulations

Gnomad4 AFR

AF:

0.00146

Gnomad4 AMR

AF:

0.000494

Gnomad4 ASJ

AF:

0.00118

Gnomad4 EAS

AF:

0.000934

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00228

Gnomad4 NFE

AF:

0.000777

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 01, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.055

DANN

Benign

0.81

DEOGEN2

Benign

0.00048

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00044

LIST_S2

Benign

0.033

M_CAP

Benign

0.00072

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.19

PROVEAN

Benign

2.4

REVEL

Benign

0.021

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.030

MutPred

0.37

Loss of methylation at K76 (P = 3e-04);

MVP

0.030

MPC

0.074

ClinPred

0.061

GERP RS

-0.34

Varity_R

0.015

gMVP

0.023

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