17-41501086-G-A

Position:

• chr17-41501086-G-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.*170C>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 0.0425 in 579,558 control chromosomes in the GnomAD database, including 687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.057 (319 hom., cov: 32)
  • Exomes 𝑓: 0.037 (368 hom.)
• Consequence: KRT13 NM_153490.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.634

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]

ENSG00000229732 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-41501086-G-A is Benign according to our data. Variant chr17-41501086-G-A is described in ClinVar as [Benign]. Clinvar id is 323071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT13	NM_153490.3	c.*170C>T		3_prime_UTR_variant	8/8	ENST00000246635.8	NP_705694.3
KRT13	NM_002274.4	c.*258C>T		3_prime_UTR_variant	7/7		NP_002265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT13	ENST00000246635	c.*170C>T		3_prime_UTR_variant	8/8	1	NM_153490.3	ENSP00000246635.3

Frequencies

GnomAD3 genomes AF: 0.0569 AC: 8656 AN: 152140 Hom.: 318 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0256

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0605

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0361

Gnomad OTH AF: 0.0416

GnomAD4 exome AF: 0.0374 AC: 15974 AN: 427300 Hom.: 368 Cov.: 4 AF XY: 0.0359 AC XY: 8178 AN XY: 227948

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.0180

Gnomad4 ASJ exome AF: 0.0407

Gnomad4 EAS exome AF: 0.0560

Gnomad4 SAS exome AF: 0.0172

Gnomad4 FIN exome AF: 0.0546

Gnomad4 NFE exome AF: 0.0355

Gnomad4 OTH exome AF: 0.0409

GnomAD4 genome AF: 0.0569 AC: 8669 AN: 152258 Hom.: 319 Cov.: 32 AF XY: 0.0567 AC XY: 4218 AN XY: 74432

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0255

Gnomad4 ASJ AF: 0.0461

Gnomad4 EAS AF: 0.0526

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.0605

Gnomad4 NFE AF: 0.0362

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0208 Hom.: 10

Bravo AF: 0.0576

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.87
CADD	Benign	0.24
DANN	Benign	0.52

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: rs3169911; hg19: chr17-39657338;