Variant 17-41054974-A-T 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_033032.3(KRTAP2-2):c.238T>A(p.Cys80Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 14)

Exomes 𝑓: 0.0016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP2-2
NM_033032.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

Variant links:

Genes affected

KRTAP2-2 (HGNC:18905): (keratin associated protein 2-2) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP2-2 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=0.21808732).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP2-2	NM_033032.3 linkuse as main transcript	c.238T>A	p.Cys80Ser	missense_variant	1/1	ENST00000398477.1	NP_149021.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP2-2	ENST00000398477.1 linkuse as main transcript	c.238T>A	p.Cys80Ser	missense_variant	1/1		NM_033032.3	ENSP00000381494	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

111876

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000696

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000279

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000215

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000934

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000266

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00156

AC:

1559

AN:

998314

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

817

AN XY:

495846

show subpopulations

Gnomad4 AFR exome

AF:

0.000487

Gnomad4 AMR exome

AF:

0.00124

Gnomad4 ASJ exome

AF:

0.00338

Gnomad4 EAS exome

AF:

0.00102

Gnomad4 SAS exome

AF:

0.00142

Gnomad4 FIN exome

AF:

0.00530

Gnomad4 NFE exome

AF:

0.00143

Gnomad4 OTH exome

AF:

0.00206

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000232

AC:

AN:

111956

Hom.:

Cov.:

AF XY:

0.000191

AC XY:

AN XY:

52228

show subpopulations

Gnomad4 AFR

AF:

0.0000693

Gnomad4 AMR

AF:

0.000278

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000216

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000934

Gnomad4 NFE

AF:

0.000266

Gnomad4 OTH

AF:

0.00

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 26, 2023

The c.238T>A (p.C80S) alteration is located in exon 1 (coding exon 1) of the KRTAP2-2 gene. This alteration results from a T to A substitution at nucleotide position 238, causing the cysteine (C) at amino acid position 80 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

Pathogenic

0.76

BayesDel_addAF

Benign

-0.0091

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

T;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

0.98

D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.4

D;D

REVEL

Uncertain

0.52

Sift

Benign

0.11

T;T

Sift4G

Uncertain

0.029

D;T

Vest4

0.27

MutPred

0.53

Gain of glycosylation at T78 (P = 0.0439);Gain of glycosylation at T78 (P = 0.0439);

MVP

0.16

ClinPred

0.86

GERP RS

4.9

Varity_R

0.24

gMVP

0.038

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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