Variant 17-41460235-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002278.3(KRT32):c.1222C>A(p.Pro408Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,914 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KRT32
NM_002278.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.56

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT32	NM_002278.3 linkuse as main transcript	c.1222C>A	p.Pro408Thr	missense_variant	7/7	ENST00000225899.4	NP_002269.3	Q14532

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT32	ENST00000225899.4 linkuse as main transcript	c.1222C>A	p.Pro408Thr	missense_variant	7/7	1	NM_002278.3	ENSP00000225899.3		Q14532

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000471

AC:

AN:

212298

Hom.:

AF XY:

0.00

AC XY:

AN XY:

114458

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000329

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1441914

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715596

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000241

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.07e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 07, 2023

The c.1222C>A (p.P408T) alteration is located in exon 7 (coding exon 7) of the KRT32 gene. This alteration results from a C to A substitution at nucleotide position 1222, causing the proline (P) at amino acid position 408 to be replaced by a threonine (T). 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

0.16

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.051

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.72

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.59

MetaSVM

Uncertain

0.42

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-6.9

REVEL

Uncertain

0.41

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.032

Polyphen

1.0

Vest4

0.41

MutPred

0.30

Loss of catalytic residue at P408 (P = 5e-04);

MVP

0.96

MPC

0.59

ClinPred

0.83

GERP RS

2.9

Varity_R

0.16

gMVP

0.39

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