17-41501085-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153490.3(KRT13):c.*171G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 571,240 control chromosomes in the GnomAD database, including 118,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (36215 hom., cov: 32)
  • Exomes 𝑓: 0.62 (82690 hom.)
• Consequence: KRT13 NM_153490.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.43

Genes affected

KRT13 (HGNC:6415): (keratin 13) 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. This type I cytokeratin is paired with keratin 4 and expressed in the suprabasal layers of non-cornified stratified epithelia. Mutations in this gene and keratin 4 have been associated with the autosomal dominant disorder White Sponge Nevus. The type I cytokeratins are clustered in a region of chromosome 17q21.2. Alternative splicing of this gene results in multiple transcript variants; however, not all variants have been described. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-41501085-C-A is Benign according to our data. Variant chr17-41501085-C-A is described in ClinVar as [Benign]. Clinvar id is 323070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT13	NM_153490.3	c.*171G>T		3_prime_UTR_variant	8/8	ENST00000246635.8
KRT13	NM_002274.4	c.*259G>T		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT13	ENST00000246635.8	c.*171G>T		3_prime_UTR_variant	8/8	1	NM_153490.3	P2
	ENST00000411759.1	n.103C>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103151 AN: 151968 Hom.: 36150 Cov.: 32

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.653

GnomAD4 exome AF: 0.623 AC: 261027 AN: 419154 Hom.: 82690 Cov.: 4 AF XY: 0.628 AC XY: 140281 AN XY: 223412

Gnomad4 AFR exome AF: 0.862

Gnomad4 AMR exome AF: 0.690

Gnomad4 ASJ exome AF: 0.620

Gnomad4 EAS exome AF: 0.528

Gnomad4 SAS exome AF: 0.721

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.594

Gnomad4 OTH exome AF: 0.624

GnomAD4 genome AF: 0.679 AC: 103276 AN: 152086 Hom.: 36215 Cov.: 32 AF XY: 0.680 AC XY: 50524 AN XY: 74338

Gnomad4 AFR AF: 0.867

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.653

Alfa AF: 0.612 Hom.: 27791

Bravo AF: 0.686

Asia WGS AF: 0.621 AC: 2162 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

White sponge nevus 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.016
Dann	Benign	0.53

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

Other links and lift over

dbSNP: rs903; hg19: chr17-39657337; COSMIC: COSV55839772; COSMIC: COSV55839772;