Variant chr17-41054971-G-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.241C>A(p.Pro81Thr) 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 0.00033 ( 0 hom., cov: 14)

Exomes 𝑓: 0.0025 ( 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: 2.13

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=0.22468159).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP2-2	NM_033032.3 linkuse as main transcript	c.241C>A	p.Pro81Thr	missense_variant	1/1	ENST00000398477.1	NP_149021.2	Q9BYT5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP2-2	ENST00000398477.1 linkuse as main transcript	c.241C>A	p.Pro81Thr	missense_variant	1/1	6	NM_033032.3	ENSP00000381494.1		Q9BYT5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

110628

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000705

Gnomad AMI

AF:

0.00140

Gnomad AMR

AF:

0.000282

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000217

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00126

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000383

Gnomad OTH

AF:

0.000719

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00250

AC:

2510

AN:

1003450

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

1326

AN XY:

498312

show subpopulations

Gnomad4 AFR exome

AF:

0.000685

Gnomad4 AMR exome

AF:

0.00183

Gnomad4 ASJ exome

AF:

0.00512

Gnomad4 EAS exome

AF:

0.00148

Gnomad4 SAS exome

AF:

0.00226

Gnomad4 FIN exome

AF:

0.00957

Gnomad4 NFE exome

AF:

0.00227

Gnomad4 OTH exome

AF:

0.00316

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000325

AC:

AN:

110714

Hom.:

Cov.:

AF XY:

0.000271

AC XY:

AN XY:

51578

show subpopulations

Gnomad4 AFR

AF:

0.0000702

Gnomad4 AMR

AF:

0.000282

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000217

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00126

Gnomad4 NFE

AF:

0.000384

Gnomad4 OTH

AF:

0.000711

Alfa

AF:

0.000448

Hom.:

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.241C>A (p.P81T) alteration is located in exon 1 (coding exon 1) of the KRTAP2-2 gene. This alteration results from a C to A substitution at nucleotide position 241, causing the proline (P) at amino acid position 81 to be replaced by a threonine (T). 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

0.29

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

T;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

0.64

D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.7

D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0040

D;D

Sift4G

Benign

0.20

T;T

Vest4

0.30

MutPred

0.47

Gain of relative solvent accessibility (P = 0.0098);Gain of relative solvent accessibility (P = 0.0098);

MVP

0.16

ClinPred

0.97

GERP RS

3.9

Varity_R

0.19

gMVP

0.067

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