Variant 17-41047021-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001123387.1(KRTAP2-1):c.247T>A(p.Ser83Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000507 in 1,500,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

KRTAP2-1
NM_001123387.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.93

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10257915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP2-1	NM_001123387.1 linkuse as main transcript	c.247T>A	p.Ser83Thr	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.247T>A	p.Ser83Thr	missense_variant	1/1	6	NM_001123387.1	ENSP00000375238.3		Q9BYU5

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

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:

0.000956

GnomAD3 exomes

AF:

0.0000155

AC:

AN:

129342

Hom.:

AF XY:

0.0000143

AC XY:

AN XY:

69894

show subpopulations

Gnomad AFR exome

AF:

0.000151

Gnomad AMR exome

AF:

0.0000417

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

AF:

0.0000237

AC:

AN:

1348060

Hom.:

Cov.:

AF XY:

0.0000196

AC XY:

AN XY:

664942

show subpopulations

Gnomad4 AFR exome

AF:

0.000357

Gnomad4 AMR exome

AF:

0.000230

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:

0.00

Gnomad4 OTH exome

AF:

0.000231

GnomAD4 genome

AF:

0.000289

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.000483

Gnomad4 AMR

AF:

0.00144

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:

0.000956

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

Sep 01, 2021

The c.247T>A (p.S83T) alteration is located in exon 1 (coding exon 1) of the KRTAP2-1 gene. This alteration results from a T to A substitution at nucleotide position 247, causing the serine (S) at amino acid position 83 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

0.15

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0058

T;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.47

M_CAP

Benign

0.0012

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.7

M;.

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.12

Sift

Benign

0.15

T;D

Sift4G

Benign

0.40

T;T

Polyphen

0.60

P;.

Vest4

0.35

MutPred

0.43

Gain of glycosylation at S82 (P = 0.0704);Gain of glycosylation at S82 (P = 0.0704);

MVP

0.088

ClinPred

0.25

GERP RS

5.8

Varity_R

0.14

gMVP

0.053

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