Variant 17-41515675-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000254043.8(KRT15):c.1044C>G(p.Asn348Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000014 ( 0 hom. )

Consequence

KRT15
ENST00000254043.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.863

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25237942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KRT15	NM_002275.4 linkuse as main transcript	c.1044C>G	p.Asn348Lys	missense_variant	6/8	ENST00000254043.8	NP_002266.3
KRT15	XM_011524784.4 linkuse as main transcript	c.1065C>G	p.Asn355Lys	missense_variant	6/8		XP_011523086.1
KRT15	XM_017024614.3 linkuse as main transcript	c.1065C>G	p.Asn355Lys	missense_variant	6/8		XP_016880103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT15	ENST00000254043.8 linkuse as main transcript	c.1044C>G	p.Asn348Lys	missense_variant	6/8	1	NM_002275.4	ENSP00000254043	P1	P19012-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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

Jan 16, 2024

The c.1044C>G (p.N348K) alteration is located in exon 6 (coding exon 6) of the KRT15 gene. This alteration results from a C to G substitution at nucleotide position 1044, causing the asparagine (N) at amino acid position 348 to be replaced by a lysine (K). 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

0.32

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

T;D;T;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.13

.;T;T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Benign

1.4

L;.;L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.2

N;D;N;D

REVEL

Benign

0.24

Sift

Benign

0.10

T;T;T;T

Sift4G

Benign

0.51

T;T;T;.

Polyphen

0.016

B;P;B;.

Vest4

0.22

MutPred

0.50

Gain of ubiquitination at N348 (P = 0.0069);.;Gain of ubiquitination at N348 (P = 0.0069);.;

MVP

0.81

MPC

0.22

ClinPred

0.27

GERP RS

3.8

Varity_R

0.14

gMVP

0.28

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over