Variant 11-1597955-C-A 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_001004325.2(KRTAP5-2):c.296G>T(p.Gly99Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000048 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

KRTAP5-2
NM_001004325.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.436

Variant links:

Genes affected

KRTAP5-2 (HGNC:23597): (keratin associated protein 5-2) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-2 links:

KRTAP5-AS1 (HGNC:):

KRTAP5-AS1 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=0.09801108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-2	NM_001004325.2 linkuse as main transcript	c.296G>T	p.Gly99Val	missense_variant	1/1	ENST00000412090.2	NP_001004325.1	Q701N4
KRTAP5-AS1	NR_021489.2 linkuse as main transcript	n.1036C>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KRTAP5-2	ENST00000412090.2 linkuse as main transcript	c.296G>T	p.Gly99Val	missense_variant	1/1	6	NM_001004325.2	ENSP00000400041.1	Q701N4
KRTAP5-AS1	ENST00000424148.1 linkuse as main transcript	n.1036C>A		non_coding_transcript_exon_variant	2/2	2
KRTAP5-AS1	ENST00000659213.1 linkuse as main transcript	n.*47C>A		downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0000480

AC:

AN:

41636

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000114

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245886

Hom.:

AF XY:

0.00000750

AC XY:

AN XY:

133254

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000552

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:

0.0000133

AC:

AN:

374974

Hom.:

Cov.:

AF XY:

0.0000106

AC XY:

AN XY:

187824

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000770

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000146

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000480

AC:

AN:

41636

Hom.:

Cov.:

AF XY:

0.0000489

AC XY:

AN XY:

20446

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000114

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Nov 09, 2021

The c.296G>T (p.G99V) alteration is located in exon 1 (coding exon 1) of the KRTAP5-2 gene. This alteration results from a G to T substitution at nucleotide position 296, causing the glycine (G) at amino acid position 99 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.0078

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.24

M_CAP

Benign

0.016

MetaRNN

Benign

0.098

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.9

PROVEAN

Benign

-0.47

REVEL

Benign

0.076

Sift4G

Benign

0.099

Polyphen

0.97

Vest4

0.25

MutPred

0.20

Gain of glycosylation at S104 (P = 0.1523);

MVP

0.24

MPC

0.11

ClinPred

0.24

GERP RS

0.56

Varity_R

0.23

gMVP

0.043

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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