Variant chr17-41515509-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002275.4(KRT15):c.1210G>A(p.Ala404Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000349 in 1,461,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

KRT15
NM_002275.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.592

Variant links:

Genes affected

KRT15 (HGNC:6421): (keratin 15) The protein encoded by this gene is a member of the keratin gene family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins. Most of the type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains and are clustered in a region on chromosome 17q21.2. [provided by RefSeq, Jul 2008]

KRT15 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3535545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KRT15	NM_002275.4 linkuse as main transcript	c.1210G>A	p.Ala404Thr	missense_variant	6/8	ENST00000254043.8
KRT15	XM_011524784.4 linkuse as main transcript	c.1231G>A	p.Ala411Thr	missense_variant	6/8
KRT15	XM_017024614.3 linkuse as main transcript	c.1231G>A	p.Ala411Thr	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT15	ENST00000254043.8 linkuse as main transcript	c.1210G>A	p.Ala404Thr	missense_variant	6/8	1	NM_002275.4	P1	P19012-1
KRT15	ENST00000393974.7 linkuse as main transcript	c.715G>A	p.Ala239Thr	missense_variant	5/7	1
KRT15	ENST00000393976.6 linkuse as main transcript	c.1210G>A	p.Ala404Thr	missense_variant	8/10	5		P1	P19012-1
KRT15	ENST00000474031.5 linkuse as main transcript	n.851G>A		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251114

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000349

AC:

AN:

1461536

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000423

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000780

Hom.:

Bravo

AF:

0.0000453

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Oct 26, 2022

The c.1210G>A (p.A404T) alteration is located in exon 6 (coding exon 6) of the KRT15 gene. This alteration results from a G to A substitution at nucleotide position 1210, causing the alanine (A) at amino acid position 404 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

0.11

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

D;D;D

Eigen

Benign

0.032

Eigen_PC

Benign

0.010

FATHMM_MKL

Benign

0.56

M_CAP

Benign

0.050

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Uncertain

0.20

MutationAssessor

Uncertain

2.5

M;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Uncertain

0.56

Sift

Benign

0.099

T;T;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.72

P;P;P

Vest4

0.18

MVP

0.84

MPC

0.26

ClinPred

0.70

GERP RS

3.7

Varity_R

0.15

gMVP

0.56

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