Variant rs2071563 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002278.3(KRT32):c.1184C>T(p.Thr395Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,613,082 control chromosomes in the GnomAD database, including 119,823 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.40 ( 12180 hom., cov: 32)

Exomes 𝑓: 0.38 ( 107643 hom. )

Consequence

KRT32
NM_002278.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.41

Variant links:

Genes affected

KRT32 (HGNC:6449): (keratin 32) The protein encoded by this gene is a member of the keratin gene family. As a type I hair keratin, it is an acidic protein which heterodimerizes with type II keratins to form hair and nails. The type I hair keratins are clustered in a region of chromosome 17q12-q21 and have the same direction of transcription. [provided by RefSeq, Jul 2008]

KRT32 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009404004).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT32	NM_002278.3 linkuse as main transcript	c.1184C>T	p.Thr395Met	missense_variant	6/7	ENST00000225899.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT32	ENST00000225899.4 linkuse as main transcript	c.1184C>T	p.Thr395Met	missense_variant	6/7	1	NM_002278.3	P1

Frequencies

GnomAD3 genomes

AF:

0.398

AC:

60403

AN:

151602

Hom.:

12157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.368

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.344

Gnomad SAS

AF:

0.262

Gnomad FIN

AF:

0.519

Gnomad MID

AF:

0.331

Gnomad NFE

AF:

0.382

Gnomad OTH

AF:

0.365

GnomAD3 exomes

AF:

0.381

AC:

95564

AN:

251104

Hom.:

18750

AF XY:

0.376

AC XY:

51026

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.421

Gnomad AMR exome

AF:

0.391

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.339

Gnomad SAS exome

AF:

0.286

Gnomad FIN exome

AF:

0.520

Gnomad NFE exome

AF:

0.381

Gnomad OTH exome

AF:

0.368

GnomAD4 exome

AF:

0.382

AC:

558727

AN:

1461360

Hom.:

107643

Cov.:

AF XY:

0.379

AC XY:

275745

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.418

Gnomad4 AMR exome

AF:

0.394

Gnomad4 ASJ exome

AF:

0.353

Gnomad4 EAS exome

AF:

0.355

Gnomad4 SAS exome

AF:

0.292

Gnomad4 FIN exome

AF:

0.504

Gnomad4 NFE exome

AF:

0.384

Gnomad4 OTH exome

AF:

0.378

GnomAD4 genome

AF:

0.399

AC:

60472

AN:

151722

Hom.:

12180

Cov.:

AF XY:

0.403

AC XY:

29906

AN XY:

74140

show subpopulations

Gnomad4 AFR

AF:

0.418

Gnomad4 AMR

AF:

0.413

Gnomad4 ASJ

AF:

0.358

Gnomad4 EAS

AF:

0.344

Gnomad4 SAS

AF:

0.261

Gnomad4 FIN

AF:

0.519

Gnomad4 NFE

AF:

0.382

Gnomad4 OTH

AF:

0.365

Alfa

AF:

0.382

Hom.:

5535

Bravo

AF:

0.391

TwinsUK

AF:

0.387

AC:

1435

ALSPAC

AF:

0.379

AC:

1462

ESP6500AA

AF:

0.411

AC:

1809

ESP6500EA

AF:

0.375

AC:

3226

ExAC

AF:

0.375

AC:

45558

Asia WGS

AF:

0.302

AC:

1052

AN:

3478

EpiCase

AF:

0.374

EpiControl

AF:

0.380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Uncertain

-0.060

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.53

Eigen

Pathogenic

0.68

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0094

MetaSVM

Benign

-1.5

MutationAssessor

Pathogenic

4.0

MutationTaster

Benign

0.28

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-5.8

REVEL

Uncertain

0.44

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.12

MPC

0.56

ClinPred

0.064

GERP RS

5.1

Varity_R

0.32

gMVP

0.71

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over