Variant 17-41054875-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033032.3(KRTAP2-2):c.337C>G(p.Pro113Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00010 ( 2 hom., cov: 15)

Exomes 𝑓: 0.000014 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP2-2
NM_033032.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.13

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05250573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP2-2	NM_033032.3 linkuse as main transcript	c.337C>G	p.Pro113Ala	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.337C>G	p.Pro113Ala	missense_variant	1/1	6	NM_033032.3	ENSP00000381494.1		Q9BYT5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

96062

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000548

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000210

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000561

AC:

AN:

124874

Hom.:

AF XY:

0.0000447

AC XY:

AN XY:

67148

show subpopulations

Gnomad AFR exome

AF:

0.00125

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000143

AC:

AN:

1325562

Hom.:

Cov.:

AF XY:

0.0000123

AC XY:

AN XY:

651698

show subpopulations

Gnomad4 AFR exome

AF:

0.000602

Gnomad4 AMR exome

AF:

0.0000355

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000310

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.49e-7

Gnomad4 OTH exome

AF:

0.0000182

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000104

AC:

AN:

96080

Hom.:

Cov.:

AF XY:

0.0000435

AC XY:

AN XY:

45986

show subpopulations

Gnomad4 AFR

AF:

0.000547

Gnomad4 AMR

AF:

0.000210

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 25, 2022

The c.337C>G (p.P113A) alteration is located in exon 2 (coding exon 2) of the KRTAP2-2 gene. This alteration results from a C to G substitution at nucleotide position 337, causing the proline (P) at amino acid position 113 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

3.7

DANN

Benign

0.86

DEOGEN2

Benign

0.00033

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.51

M_CAP

Benign

0.0097

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.0

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.13

REVEL

Benign

0.064

Sift

Benign

1.0

Sift4G

Uncertain

0.055

Vest4

0.30

MutPred

0.34

Loss of glycosylation at P113 (P = 0.0566);

MVP

0.092

ClinPred

0.024

GERP RS

2.7

Varity_R

0.023

gMVP

0.029

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