Variant 11-1630169-G-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_001001480.3(KRTAP5-5):c.329G>T(p.Gly110Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000247 in 1,415,630 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 16)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

KRTAP5-5
NM_001001480.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.237

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026443154).

BP6

Variant 11-1630169-G-T is Benign according to our data. Variant chr11-1630169-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3117112.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.329G>T	p.Gly110Val	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.329G>T	p.Gly110Val	missense_variant	1/1	6	NM_001001480.3	ENSP00000382584.2		Q701N2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

104848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000259

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000554

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000205

Gnomad OTH

AF:

0.000709

GnomAD3 exomes

AF:

0.0000441

AC:

AN:

226770

Hom.:

AF XY:

0.0000644

AC XY:

AN XY:

124214

show subpopulations

Gnomad AFR exome

AF:

0.0000786

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000475

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000188

GnomAD4 exome

AF:

0.0000183

AC:

AN:

1310690

Hom.:

Cov.:

AF XY:

0.0000231

AC XY:

AN XY:

649814

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000345

Gnomad4 SAS exome

AF:

0.0000409

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000196

Gnomad4 OTH exome

AF:

0.000156

GnomAD4 genome

AF:

0.000105

AC:

AN:

104940

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

50886

show subpopulations

Gnomad4 AFR

AF:

0.000258

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000555

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000205

Gnomad4 OTH

AF:

0.000699

Alfa

AF:

0.0000713

Hom.:

ExAC

AF:

0.000124

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

Sep 26, 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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.2

DANN

Benign

0.43

DEOGEN2

Benign

0.032

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.056

M_CAP

Benign

0.0041

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.2

PROVEAN

Benign

0.050

REVEL

Benign

0.12

Sift

Benign

0.035

Sift4G

Benign

0.21

Polyphen

0.96

Vest4

0.15

MVP

0.32

MPC

0.24

ClinPred

0.032

GERP RS

1.7

Varity_R

0.031

gMVP

0.11

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