Variant 17-41047126-G-A 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_001123387.1(KRTAP2-1):c.142C>T(p.Pro48Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000727 in 151,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000061 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP2-1
NM_001123387.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.506

Variant links:

Genes affected

KRTAP2-1 (HGNC:16775): (keratin associated protein 2-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP2-1 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=0.009284943).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP2-1	NM_001123387.1 linkuse as main transcript	c.142C>T	p.Pro48Ser	missense_variant	1/1	ENST00000391419.3	NP_001116859.1	Q9BYU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP2-1	ENST00000391419.3 linkuse as main transcript	c.142C>T	p.Pro48Ser	missense_variant	1/1	6	NM_001123387.1	ENSP00000375238.3		Q9BYU5

Frequencies

GnomAD3 genomes

AF:

0.0000727

AC:

AN:

151228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000267

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000811

AC:

AN:

61642

Hom.:

AF XY:

0.0000322

AC XY:

AN XY:

31040

show subpopulations

Gnomad AFR exome

AF:

0.000891

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:

0.0000609

AC:

AN:

1199476

Hom.:

Cov.:

AF XY:

0.0000580

AC XY:

AN XY:

586254

show subpopulations

Gnomad4 AFR exome

AF:

0.000411

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000651

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000727

AC:

AN:

151346

Hom.:

Cov.:

AF XY:

0.0000676

AC XY:

AN XY:

73936

show subpopulations

Gnomad4 AFR

AF:

0.000267

Gnomad4 AMR

AF:

0.00

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

Alfa

AF:

0.000222

Hom.:

ExAC

AF:

0.0000951

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

Jun 16, 2024

The c.142C>T (p.P48S) alteration is located in exon 1 (coding exon 1) of the KRTAP2-1 gene. This alteration results from a C to T substitution at nucleotide position 142, causing the proline (P) at amino acid position 48 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

Benign

0.081

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0095

T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.64

M_CAP

Benign

0.0057

MetaRNN

Benign

0.0093

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.24

N;.

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.33

N;N

REVEL

Benign

0.042

Sift

Benign

0.48

T;T

Sift4G

Benign

0.73

T;T

Polyphen

0.19

B;.

Vest4

0.20

MutPred

0.25

Loss of glycosylation at T45 (P = 0.0494);Loss of glycosylation at T45 (P = 0.0494);

MVP

0.12

ClinPred

0.029

GERP RS

3.7

Varity_R

0.016

gMVP

0.076

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