Variant chr21-30592588-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_181605.4(KRTAP6-3):c.143G>T(p.Gly48Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00548 in 1,611,566 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 41 hom. )

Consequence

KRTAP6-3
NM_181605.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.59

Variant links:

Genes affected

KRTAP6-3 (HGNC:18933): (keratin associated protein 6-3) Predicted to be involved in keratinization. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP6-3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009274393).

BP6

Variant 21-30592588-G-T is Benign according to our data. Variant chr21-30592588-G-T is described in ClinVar as [Benign]. Clinvar id is 773370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP6-3	NM_181605.4 linkuse as main transcript	c.143G>T	p.Gly48Val	missense_variant	1/1	ENST00000391624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP6-3	ENST00000391624.1 linkuse as main transcript	c.143G>T	p.Gly48Val	missense_variant	1/1	6	NM_181605.4	ENSP00000375482.2		Q3LI67

Frequencies

GnomAD3 genomes

AF:

0.00467

AC:

710

AN:

151904

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000846

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00722

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.0159

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00664

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.00470

AC:

1182

AN:

251292

Hom.:

AF XY:

0.00460

AC XY:

625

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.00635

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.0128

Gnomad NFE exome

AF:

0.00641

Gnomad OTH exome

AF:

0.00571

GnomAD4 exome

AF:

0.00557

AC:

8124

AN:

1459546

Hom.:

Cov.:

AF XY:

0.00541

AC XY:

3927

AN XY:

726122

show subpopulations

Gnomad4 AFR exome

AF:

0.000749

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.00740

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000546

Gnomad4 FIN exome

AF:

0.0127

Gnomad4 NFE exome

AF:

0.00613

Gnomad4 OTH exome

AF:

0.00456

GnomAD4 genome

AF:

0.00468

AC:

711

AN:

152020

Hom.:

Cov.:

AF XY:

0.00479

AC XY:

356

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.000844

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00722

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000624

Gnomad4 FIN

AF:

0.0159

Gnomad4 NFE

AF:

0.00665

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.00553

Hom.:

Bravo

AF:

0.00357

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00605

AC:

ExAC

AF:

0.00452

AC:

549

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00676

EpiControl

AF:

0.00658

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.64

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.80

MetaRNN

Benign

0.0093

MetaSVM

Benign

-1.1

REVEL

Benign

0.098

Sift4G

Pathogenic

0.0

Vest4

0.74

MVP

0.043

MPC

0.066

ClinPred

0.026

GERP RS

1.0

gMVP

0.19

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