Genetic Variant NM_153490.3:c.1270+8A>T (chr17-41501711-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153490.3(KRT13):c.1270+8A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,431,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

KRT13
NM_153490.3 splice_region, intron

Scores

Splicing: ADA: 0.00004759

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.257

Publications

0 publications found

Variant links:

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

KRT13 links:

ENSG00000229732 (HGNC:):

ENSG00000229732 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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.1270+8A>T		splice_region intron	N/A	NP_705694.3	P13646-1
	KRT13	NM_002274.4		c.1245-349A>T		intron	N/A	NP_002265.3	P13646-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KRT13	ENST00000246635.8	TSL:1 MANE Select	c.1270+8A>T	splice_region intron	N/A	ENSP00000246635.3	P13646-1
KRT13	ENST00000336861.7	TSL:1	c.1245-349A>T	intron	N/A	ENSP00000336604.3	P13646-3
KRT13	ENST00000970738.1		c.1267+8A>T	splice_region intron	N/A	ENSP00000640797.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1431586

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

708848

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32938

American (AMR)

AF:

0.00

AC:

AN:

40354

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25558

East Asian (EAS)

AF:

0.00

AC:

AN:

38452

South Asian (SAS)

AF:

0.00

AC:

AN:

81626

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

9.12e-7

AC:

AN:

1096236

Other (OTH)

AF:

0.00

AC:

AN:

59282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.82

(source)

DANN

Benign

0.82

PhyloP100

-0.26

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000048

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over