Variant 11-1622036-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001347674.1(KRTAP5-4):c.58G>A(p.Gly20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000184 in 1,355,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

KRTAP5-4
NM_001347674.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.65

Variant links:

Genes affected

KRTAP5-4 (HGNC:23599): (keratin associated protein 5-4) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028504133).

BP6

Variant 11-1622036-C-T is Benign according to our data. Variant chr11-1622036-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3117108.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-4	NM_001347674.1 linkuse as main transcript	c.58G>A	p.Gly20Ser	missense_variant	1/1	ENST00000399682.1	NP_001334603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP5-4	ENST00000399682.1 linkuse as main transcript	c.58G>A	p.Gly20Ser	missense_variant	1/1		NM_001347674.1	ENSP00000382590	P1

Frequencies

GnomAD3 genomes

AF:

0.0000387

AC:

AN:

129140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000582

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:

0.00435

Gnomad NFE

AF:

0.0000340

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000333

AC:

AN:

239992

Hom.:

AF XY:

0.0000229

AC XY:

AN XY:

130926

show subpopulations

Gnomad AFR exome

AF:

0.000143

Gnomad AMR exome

AF:

0.000119

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:

0.0000184

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000163

AC:

AN:

1226128

Hom.:

Cov.:

AF XY:

0.00000983

AC XY:

AN XY:

610382

show subpopulations

Gnomad4 AFR exome

AF:

0.0000729

Gnomad4 AMR exome

AF:

0.000104

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000269

Gnomad4 FIN exome

AF:

0.0000438

Gnomad4 NFE exome

AF:

0.0000107

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000387

AC:

AN:

129228

Hom.:

Cov.:

AF XY:

0.0000475

AC XY:

AN XY:

63210

show subpopulations

Gnomad4 AFR

AF:

0.0000581

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:

0.0000340

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000356

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.7

DANN

Benign

0.53

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0062

M_CAP

Benign

0.0028

MetaRNN

Benign

0.029

T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

PROVEAN

Benign

2.0

N;.

REVEL

Benign

0.030

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.67

T;T

Vest4

0.052

MutPred

0.16

Gain of phosphorylation at G20 (P = 0.026);Gain of phosphorylation at G20 (P = 0.026);

MVP

0.030

MPC

0.026

ClinPred

0.021

GERP RS

-3.8

gMVP

0.017

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