17-41501281-C-G

Variant names:

• chr17-41501281-C-G
• rs550693344
• NM_153490.3:c.1352G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153490.3(KRT13):​c.1352G>C​(p.Arg451Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,417,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R451H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: KRT13 NM_153490.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 1 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3137101).

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.1352G>C	p.Arg451Pro	missense	Exon 8 of 8	NP_705694.3	P13646-1
	KRT13	NM_002274.4		c.*63G>C		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.1352G>C	p.Arg451Pro	missense	Exon 8 of 8	ENSP00000246635.3	P13646-1
	KRT13	ENST00000336861.7	TSL:1	c.*63G>C		3_prime_UTR	Exon 7 of 7	ENSP00000336604.3	P13646-3
	KRT13	ENST00000970738.1		c.1349G>C	p.Arg450Pro	missense	Exon 8 of 8	ENSP00000640797.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000543 AC: 1 AN: 184110 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000381

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1417660 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 700684

African (AFR) AF: 0.00 AC: 0 AN: 32960

American (AMR) AF: 0.0000270 AC: 1 AN: 37042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25274

East Asian (EAS) AF: 0.00 AC: 0 AN: 38148

South Asian (SAS) AF: 0.00 AC: 0 AN: 80430

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088886

Other (OTH) AF: 0.00 AC: 0 AN: 58862

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	18
DANN	Benign	0.82
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.4
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.10	N
REVEL	Uncertain	0.37
Sift	Benign	0.052	T
Sift4G	Benign	0.29	T
Polyphen		0.99	D
Vest4		0.40
MutPred		0.32		Loss of MoRF binding (P = 0.0335)
MVP		0.86
MPC		0.14
ClinPred		0.19	T
GERP RS		2.3
Varity_R		0.23
gMVP		0.093

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: rs550693344; hg19: chr17-39657533;