Variant chr11-71582755-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001005405.3(KRTAP5-11):c.83G>C(p.Cys28Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000541 in 1,530,050 control chromosomes in the GnomAD database, including 2 homozygotes. 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 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 2 hom. )

Consequence

KRTAP5-11
NM_001005405.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.245

Variant links:

Genes affected

KRTAP5-11 (HGNC:23606): (keratin associated protein 5-11) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-11 links:

KRTAP5-11 (HGNC:):

KRTAP5-11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14116338).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-11	NM_001005405.3 linkuse as main transcript	c.83G>C	p.Cys28Ser	missense_variant	1/1	ENST00000398530.1	NP_001005405.1	Q6L8G4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP5-11	ENST00000398530.1 linkuse as main transcript	c.83G>C	p.Cys28Ser	missense_variant	1/1	6	NM_001005405.3	ENSP00000381541.1		Q6L8G4
KRTAP5-11	ENST00000526239.1 linkuse as main transcript	n.381-598G>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000330

AC:

AN:

133234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000250

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.000100

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000524

Gnomad OTH

AF:

0.000535

GnomAD3 exomes

AF:

0.000271

AC:

AN:

250486

Hom.:

AF XY:

0.000273

AC XY:

AN XY:

135624

show subpopulations

Gnomad AFR exome

AF:

0.0000633

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000432

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000561

AC:

783

AN:

1396816

Hom.:

Cov.:

AF XY:

0.000558

AC XY:

388

AN XY:

695704

show subpopulations

Gnomad4 AFR exome

AF:

0.000135

Gnomad4 AMR exome

AF:

0.000211

Gnomad4 ASJ exome

AF:

0.0000411

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000294

Gnomad4 FIN exome

AF:

0.000100

Gnomad4 NFE exome

AF:

0.000665

Gnomad4 OTH exome

AF:

0.000458

GnomAD4 genome

AF:

0.000330

AC:

AN:

133234

Hom.:

Cov.:

AF XY:

0.000306

AC XY:

AN XY:

65374

show subpopulations

Gnomad4 AFR

AF:

0.000250

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.000100

Gnomad4 NFE

AF:

0.000524

Gnomad4 OTH

AF:

0.000535

Alfa

AF:

0.000503

Hom.:

Bravo

AF:

0.000298

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000467

AC:

ExAC

AF:

0.000201

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000593

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

Dec 19, 2022

The c.83G>C (p.C28S) alteration is located in exon 1 (coding exon 1) of the KRTAP5-11 gene. This alteration results from a G to C substitution at nucleotide position 83, causing the cysteine (C) at amino acid position 28 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

0.14

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.1

DANN

Benign

0.86

DEOGEN2

Benign

0.091

.;T

Eigen

Benign

0.15

Eigen_PC

Benign

0.034

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.20

T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

.;L

PROVEAN

Pathogenic

-4.9

.;D

REVEL

Benign

0.046

Sift

Pathogenic

0.0

.;D

Sift4G

Uncertain

0.055

T;D

Polyphen

0.99

.;D

Vest4

0.31

MutPred

0.27

Gain of glycosylation at C28 (P = 0.0012);Gain of glycosylation at C28 (P = 0.0012);

MVP

0.20

MPC

0.011

ClinPred

0.089

GERP RS

2.1

Varity_R

0.58

gMVP

0.025

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