chr17-41501085-C-A

Variant names:

• chr17-41501085-C-A
• rs903
• NM_153490.3:c.*171G>T

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -5.43
• Publications: 16 publications found

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]

KRT13 Gene-Disease associations (from GenCC):

• white sponge nevus 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary mucosal leukokeratosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000229732 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153490.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT13	NM_153490.3	MANE Select	c.*171G>T		3_prime_UTR	Exon 8 of 8	NP_705694.3	P13646-1
	KRT13	NM_002274.4		c.*259G>T		3_prime_UTR	Exon 7 of 7	NP_002265.3	P13646-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT13	ENST00000246635.8	TSL:1 MANE Select	c.*171G>T		3_prime_UTR	Exon 8 of 8	ENSP00000246635.3	P13646-1
	KRT13	ENST00000336861.7	TSL:1	c.*259G>T		3_prime_UTR	Exon 7 of 7	ENSP00000336604.3	P13646-3
	KRT13	ENST00000970738.1		c.*171G>T		3_prime_UTR	Exon 8 of 8	ENSP00000640797.1

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

African (AFR) AF: 0.862 AC: 10066 AN: 11680

American (AMR) AF: 0.690 AC: 15299 AN: 22170

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 8198 AN: 13224

East Asian (EAS) AF: 0.528 AC: 13794 AN: 26140

South Asian (SAS) AF: 0.721 AC: 36134 AN: 50114

European-Finnish (FIN) AF: 0.625 AC: 18664 AN: 29878

Middle Eastern (MID) AF: 0.701 AC: 1286 AN: 1834

European-Non Finnish (NFE) AF: 0.594 AC: 143204 AN: 241058

Other (OTH) AF: 0.624 AC: 14382 AN: 23056

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

African (AFR) AF: 0.867 AC: 35975 AN: 41496

American (AMR) AF: 0.649 AC: 9923 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2082 AN: 3470

East Asian (EAS) AF: 0.493 AC: 2542 AN: 5158

South Asian (SAS) AF: 0.716 AC: 3454 AN: 4822

European-Finnish (FIN) AF: 0.627 AC: 6622 AN: 10562

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40453 AN: 67966

Other (OTH) AF: 0.653 AC: 1380 AN: 2114

Alfa AF: 0.626 Hom.: 43464

Bravo AF: 0.686

Asia WGS AF: 0.621 AC: 2162 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	White sponge nevus 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.016
DANN	Benign	0.53
PhyloP100		-5.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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