chr17-41514055-G-T

Position:

• chr17-41514055-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000254043.8(KRT15):​c.1339C>A​(p.Gln447Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRT15 ENST00000254043.8 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.26

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.088697135).
• BP6: Variant 17-41514055-G-T is Benign according to our data. Variant chr17-41514055-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2228851.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT15	NM_002275.4	c.1339C>A	p.Gln447Lys	missense_variant	8/8	ENST00000254043.8	NP_002266.3
KRT15	XM_011524784.4	c.1360C>A	p.Gln454Lys	missense_variant	8/8		XP_011523086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT15	ENST00000254043.8	c.1339C>A	p.Gln447Lys	missense_variant	8/8	1	NM_002275.4	ENSP00000254043	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 03, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	11
DANN	Benign	0.14
DEOGEN2	Benign	0.011	T;T;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.0093	N
LIST_S2	Benign	0.59	.;T;T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N;.;N
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	1.6	N;N;N
REVEL	Benign	0.19
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.10
MutPred		0.41		Gain of methylation at Q447 (P = 0.0144);.;Gain of methylation at Q447 (P = 0.0144);
MVP		0.66
MPC		0.13
ClinPred		0.035	T
GERP RS		5.8
Varity_R		0.063
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-39670307;