Variant 21-30755305-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_181619.2(KRTAP21-1):c.74G>A(p.Gly25Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000713 in 1,613,342 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00075 ( 1 hom. )

Consequence

KRTAP21-1
NM_181619.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.611

Variant links:

Genes affected

KRTAP21-1 (HGNC:18945): (keratin associated protein 21-1) Predicted to be involved in hair follicle development. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP21-1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.129177).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP21-1	NM_181619.2 linkuse as main transcript	c.74G>A	p.Gly25Asp	missense_variant	1/1	ENST00000335093.5	NP_853650.1	Q3LI58

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP21-1	ENST00000335093.5 linkuse as main transcript	c.74G>A	p.Gly25Asp	missense_variant	1/1	6	NM_181619.2	ENSP00000335566.3		Q3LI58

Frequencies

GnomAD3 genomes

AF:

0.000382

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000304

AC:

AN:

250336

Hom.:

AF XY:

0.000244

AC XY:

AN XY:

135314

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000559

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000748

AC:

1093

AN:

1461312

Hom.:

Cov.:

AF XY:

0.000703

AC XY:

511

AN XY:

726882

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000949

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000382

AC:

AN:

152030

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000328

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000557

Hom.:

Bravo

AF:

0.000457

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00182

AC:

ExAC

AF:

0.000231

AC:

EpiCase

AF:

0.00104

EpiControl

AF:

0.000711

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

Dec 12, 2023

The c.74G>A (p.G25D) alteration is located in exon 1 (coding exon 1) of the KRTAP21-1 gene. This alteration results from a G to A substitution at nucleotide position 74, causing the glycine (G) at amino acid position 25 to be replaced by an aspartic acid (D). 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

0.31

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Uncertain

0.070

CADD

Benign

6.6

DANN

Benign

0.50

DEOGEN2

Benign

0.11

Eigen

Benign

-0.053

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.34

M_CAP

Benign

0.0052

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.96

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.30

Sift

Benign

0.74

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.33

MVP

0.18

MPC

0.031

ClinPred

0.11

GERP RS

4.1

Varity_R

0.12

gMVP

0.067

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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