Variant 11-1629952-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001001480.3(KRTAP5-5):c.112T>C(p.Cys38Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00442 in 1,516,012 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0050 ( 11 hom., cov: 29)

Exomes 𝑓: 0.0044 ( 21 hom. )

Consequence

KRTAP5-5
NM_001001480.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

Variant links:

Genes affected

KRTAP5-5 (HGNC:23601): (keratin associated protein 5-5) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067453682).

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-5	NM_001001480.3 linkuse as main transcript	c.112T>C	p.Cys38Arg	missense_variant	1/1	ENST00000399676.4	NP_001001480.2	Q701N2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP5-5	ENST00000399676.4 linkuse as main transcript	c.112T>C	p.Cys38Arg	missense_variant	1/1	6	NM_001001480.3	ENSP00000382584.2		Q701N2

Frequencies

GnomAD3 genomes

AF:

0.00501

AC:

716

AN:

142852

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00521

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00448

Gnomad ASJ

AF:

0.0158

Gnomad EAS

AF:

0.00139

Gnomad SAS

AF:

0.00100

Gnomad FIN

AF:

0.00413

Gnomad MID

AF:

0.0104

Gnomad NFE

AF:

0.00518

Gnomad OTH

AF:

0.00565

GnomAD3 exomes

AF:

0.00307

AC:

729

AN:

237490

Hom.:

AF XY:

0.00287

AC XY:

372

AN XY:

129574

show subpopulations

Gnomad AFR exome

AF:

0.00362

Gnomad AMR exome

AF:

0.00264

Gnomad ASJ exome

AF:

0.00681

Gnomad EAS exome

AF:

0.000279

Gnomad SAS exome

AF:

0.000205

Gnomad FIN exome

AF:

0.00394

Gnomad NFE exome

AF:

0.00380

Gnomad OTH exome

AF:

0.00458

GnomAD4 exome

AF:

0.00435

AC:

5976

AN:

1373056

Hom.:

Cov.:

132

AF XY:

0.00428

AC XY:

2915

AN XY:

681452

show subpopulations

Gnomad4 AFR exome

AF:

0.00476

Gnomad4 AMR exome

AF:

0.00297

Gnomad4 ASJ exome

AF:

0.0109

Gnomad4 EAS exome

AF:

0.000541

Gnomad4 SAS exome

AF:

0.000561

Gnomad4 FIN exome

AF:

0.00323

Gnomad4 NFE exome

AF:

0.00463

Gnomad4 OTH exome

AF:

0.00539

GnomAD4 genome

AF:

0.00502

AC:

718

AN:

142956

Hom.:

Cov.:

AF XY:

0.00491

AC XY:

342

AN XY:

69602

show subpopulations

Gnomad4 AFR

AF:

0.00525

Gnomad4 AMR

AF:

0.00448

Gnomad4 ASJ

AF:

0.0158

Gnomad4 EAS

AF:

0.00140

Gnomad4 SAS

AF:

0.00100

Gnomad4 FIN

AF:

0.00413

Gnomad4 NFE

AF:

0.00519

Gnomad4 OTH

AF:

0.00561

Alfa

AF:

0.00311

Hom.:

ExAC

AF:

0.000970

AC:

114

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 17, 2021

The c.112T>C (p.C38R) alteration is located in exon 1 (coding exon 1) of the KRTAP5-5 gene. This alteration results from a T to C substitution at nucleotide position 112, causing the cysteine (C) at amino acid position 38 to be replaced by an arginine (R). 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

0.19

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.59

DEOGEN2

Benign

0.080

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.38

M_CAP

Benign

0.017

MetaRNN

Benign

0.0067

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.088

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

0.068

Vest4

0.34

MVP

0.20

MPC

0.33

ClinPred

0.082

GERP RS

2.5

Varity_R

0.66

gMVP

0.50

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