Variant 11-1630163-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001001480.3(KRTAP5-5):c.323C>G(p.Ala108Gly) 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 14)

Exomes 𝑓: 0.00013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP5-5
NM_001001480.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.103

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03235045).

BP6

Variant 11-1630163-C-G is Benign according to our data. Variant chr11-1630163-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3117111.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-5	NM_001001480.3 linkuse as main transcript	c.323C>G	p.Ala108Gly	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.323C>G	p.Ala108Gly	missense_variant	1/1	6	NM_001001480.3	ENSP00000382584.2		Q701N2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

75064

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000794

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000830

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000957

Gnomad FIN

AF:

0.000689

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000550

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000895

AC:

AN:

223374

Hom.:

AF XY:

0.00

AC XY:

AN XY:

122418

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000109

Gnomad EAS exome

AF:

0.0000611

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000128

AC:

171

AN:

1339268

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

107

AN XY:

664182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000151

Gnomad4 ASJ exome

AF:

0.0000437

Gnomad4 EAS exome

AF:

0.000115

Gnomad4 SAS exome

AF:

0.000973

Gnomad4 FIN exome

AF:

0.000265

Gnomad4 NFE exome

AF:

0.0000686

Gnomad4 OTH exome

AF:

0.0000747

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000612

AC:

AN:

75138

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

35962

show subpopulations

Gnomad4 AFR

AF:

0.000791

Gnomad4 AMR

AF:

0.000829

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000959

Gnomad4 FIN

AF:

0.000689

Gnomad4 NFE

AF:

0.000550

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0108

Hom.:

ExAC

AF:

0.0000166

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

Aug 30, 2021

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

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.3

DANN

Benign

0.27

DEOGEN2

Benign

0.0044

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.026

M_CAP

Benign

0.012

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.7

PROVEAN

Benign

-0.84

REVEL

Benign

0.10

Sift

Uncertain

0.025

Sift4G

Benign

0.90

Polyphen

0.0

Vest4

0.036

MutPred

0.16

Loss of ubiquitination at K106 (P = 0.0924);

MVP

0.11

MPC

0.19

ClinPred

0.075

GERP RS

1.7

Varity_R

0.063

gMVP

0.043

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