NM_153490.3:c.1273dupA

Variant names:

• chr17-41501359-C-CT
• rs375760692
• NM_153490.3:c.1273dupA

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_153490.3(KRT13):​c.1273dupA​(p.Ser425LysfsTer6) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,558,802 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. S425S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: KRT13 NM_153490.3 frameshift, splice_region
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.89
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 17-41501359-C-CT is Benign according to our data. Variant chr17-41501359-C-CT is described in ClinVar as Benign. ClinVar VariationId is 753332.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 20 AD gene.

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.1273dupA	p.Ser425LysfsTer6	frameshift splice_region	Exon 8 of 8	NP_705694.3	P13646-1
	KRT13	NM_002274.4		c.1247dupA	p.Arg417AlafsTer82	frameshift splice_region	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.1273dupA	p.Ser425LysfsTer6	frameshift splice_region	Exon 8 of 8	ENSP00000246635.3	P13646-1
	KRT13	ENST00000336861.7	TSL:1	c.1247dupA	p.Arg417AlafsTer82	frameshift splice_region	Exon 7 of 7	ENSP00000336604.3	P13646-3
	KRT13	ENST00000970738.1		c.1270dupA	p.Ser424LysfsTer6	frameshift splice_region	Exon 8 of 8	ENSP00000640797.1

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000468 AC: 78 AN: 166640 AF XY: 0.000513

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00559

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000122 AC: 171 AN: 1406518 Hom.: 0 Cov.: 30 AF XY: 0.000135 AC XY: 94 AN XY: 694370

African (AFR) AF: 0.00 AC: 0 AN: 32456

American (AMR) AF: 0.00 AC: 0 AN: 36030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25192

East Asian (EAS) AF: 0.00341 AC: 127 AN: 37256

South Asian (SAS) AF: 0.000414 AC: 33 AN: 79696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00000370 AC: 4 AN: 1082064

Other (OTH) AF: 0.000120 AC: 7 AN: 58354

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152284 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74454

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00368 AC: 19 AN: 5162

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000116 Hom.: 0

Bravo AF: 0.000336

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9
Mutation Taster		=95/105	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs375760692; hg19: chr17-39657611;