Genetic Variant NM_153490.3:c.*274T>C (chr17-41500982-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_153490.3(KRT13):c.*274T>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00053 in 362,096 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

KRT13
NM_153490.3 splice_region

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.161

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 17-41500982-A-G is Benign according to our data. Variant chr17-41500982-A-G is described in ClinVar as Benign. ClinVar VariationId is 892504.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 164 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KRT13	NM_153490.3	MANE Select	c.*274T>C	splice_region	Exon 8 of 8	NP_705694.3	P13646-1
KRT13	NM_153490.3	MANE Select	c.*274T>C	3_prime_UTR	Exon 8 of 8	NP_705694.3	P13646-1
KRT13	NM_002274.4		c.*362T>C	splice_region	Exon 7 of 7	NP_002265.3	P13646-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KRT13	ENST00000246635.8	TSL:1 MANE Select	c.*274T>C	splice_region	Exon 8 of 8	ENSP00000246635.3	P13646-1
KRT13	ENST00000336861.7	TSL:1	c.*362T>C	splice_region	Exon 7 of 7	ENSP00000336604.3	P13646-3
KRT13	ENST00000246635.8	TSL:1 MANE Select	c.*274T>C	3_prime_UTR	Exon 8 of 8	ENSP00000246635.3	P13646-1

Frequencies

GnomAD3 genomes

AF:

0.00104

AC:

158

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00352

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD4 exome

AF:

0.000133

AC:

AN:

209754

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

113668

show subpopulations

African (AFR)

AF:

0.00373

AC:

AN:

5902

American (AMR)

AF:

0.000364

AC:

AN:

11002

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5194

East Asian (EAS)

AF:

0.00

AC:

AN:

9856

South Asian (SAS)

AF:

0.00

AC:

AN:

39746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

734

European-Non Finnish (NFE)

AF:

0.0000170

AC:

AN:

117504

Other (OTH)

AF:

0.00

AC:

AN:

10638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00108

AC:

164

AN:

152342

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00366

AC:

152

AN:

41580

American (AMR)

AF:

0.000457

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68034

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000712

Hom.:

Bravo

AF:

0.00113

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

White sponge nevus 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.5

(source)

DANN

Benign

0.66

PhyloP100

-0.16

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over