Variant chr21-30613795-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181602.2(KRTAP6-1):c.110G>A(p.Cys37Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000372 in 1,613,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00038 ( 0 hom. )

Consequence

KRTAP6-1
NM_181602.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.754

Variant links:

Genes affected

KRTAP6-1 (HGNC:18931): (keratin associated protein 6-1) Predicted to be involved in keratinization. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP6-1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03202042).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP6-1	NM_181602.2 link	c.110G>A	p.Cys37Tyr	missense_variant	1/1	ENST00000329122.2	NP_853633.1	Q3LI64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP6-1	ENST00000329122.2 link	c.110G>A	p.Cys37Tyr	missense_variant	1/1	6	NM_181602.2	ENSP00000332690.2		Q3LI64

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000378

AC:

AN:

251304

Hom.:

AF XY:

0.000442

AC XY:

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000546

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000380

AC:

555

AN:

1461376

Hom.:

Cov.:

AF XY:

0.000413

AC XY:

300

AN XY:

726980

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000244

Gnomad4 FIN exome

AF:

0.000487

Gnomad4 NFE exome

AF:

0.000417

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000296

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000381

Hom.:

Bravo

AF:

0.000355

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000478

AC:

EpiCase

AF:

0.00115

EpiControl

AF:

0.000652

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

Sep 27, 2021

The c.110G>A (p.C37Y) alteration is located in exon 1 (coding exon 1) of the KRTAP6-1 gene. This alteration results from a G to A substitution at nucleotide position 110, causing the cysteine (C) at amino acid position 37 to be replaced by a tyrosine (Y). 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

0.089

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.6

DANN

Benign

0.77

DEOGEN2

Benign

0.064

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.30

M_CAP

Benign

0.0018

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.99

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.15

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.15

MVP

0.24

MPC

0.24

ClinPred

0.019

GERP RS

1.2

Varity_R

0.39

gMVP

0.041

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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