12-52517617-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000424.4(KRT5):c.1065A>C(p.Thr355Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,614,020 control chromosomes in the GnomAD database, including 15,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1803 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13271 hom. )

Consequence

KRT5
NM_000424.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: -6.08

Publications

19 publications found

Variant links:

Genes affected

KRT5 (HGNC:6442): (keratin 5) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in the basal layer of the epidermis with family member KRT14. Mutations in these genes have been associated with a complex of diseases termed epidermolysis bullosa simplex. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [provided by RefSeq, Jul 2008]

KRT5 Gene-Disease associations (from GenCC):

Dowling-Degos disease
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
epidermolysis bullosa simplex 1A, generalized severe
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Ambry Genetics
epidermolysis bullosa simplex 2F, with mottled pigmentation
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia, G2P
Dowling-Degos disease 1
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
epidermolysis bullosa simplex 1B, generalized intermediate
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
epidermolysis bullosa simplex 1C, localized
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
epidermolysis bullosa simplex 2B, generalized intermediate
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
epidermolysis bullosa simplex 2d, generalized, intermediate or severe, autosomal recessive
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
epidermolysis bullosa simplex 2E, with migratory circinate erythema
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KRT5 links:

ENSG00000303382 (HGNC:):

ENSG00000303382 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 12-52517617-T-G is Benign according to our data. Variant chr12-52517617-T-G is described in ClinVar as Benign. ClinVar VariationId is 66198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000424.4. 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
	KRT5	NM_000424.4	MANE Select	c.1065A>C	p.Thr355Thr	synonymous	Exon 5 of 9	NP_000415.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KRT5	ENST00000252242.9	TSL:1 MANE Select	c.1065A>C	p.Thr355Thr	synonymous	Exon 5 of 9	ENSP00000252242.4
KRT5	ENST00000552629.5	TSL:1	n.1163A>C		non_coding_transcript_exon	Exon 5 of 7
KRT5	ENST00000548409.5	TSL:3	c.186A>C	p.Thr62Thr	synonymous	Exon 2 of 5	ENSP00000448767.1

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22833

AN:

152076

Hom.:

1797

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.0336

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.182

GnomAD2 exomes

AF:

0.132

AC:

33240

AN:

251484

AF XY:

0.131

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.151

Gnomad ASJ exome

AF:

0.205

Gnomad EAS exome

AF:

0.0303

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.145

GnomAD4 exome

AF:

0.131

AC:

191433

AN:

1461826

Hom.:

13271

Cov.:

AF XY:

0.130

AC XY:

94672

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.180

AC:

6027

AN:

33478

American (AMR)

AF:

0.154

AC:

6866

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

5206

AN:

26134

East Asian (EAS)

AF:

0.0247

AC:

979

AN:

39698

South Asian (SAS)

AF:

0.102

AC:

8831

AN:

86258

European-Finnish (FIN)

AF:

0.132

AC:

7067

AN:

53418

Middle Eastern (MID)

AF:

0.189

AC:

1091

AN:

5766

European-Non Finnish (NFE)

AF:

0.132

AC:

147073

AN:

1111958

Other (OTH)

AF:

0.137

AC:

8293

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

9677

19354

29030

38707

48384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5258

10516

15774

21032

26290

<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:

0.150

AC:

22864

AN:

152194

Hom.:

1803

Cov.:

AF XY:

0.150

AC XY:

11161

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.179

AC:

7436

AN:

41522

American (AMR)

AF:

0.178

AC:

2720

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

686

AN:

3468

East Asian (EAS)

AF:

0.0333

AC:

172

AN:

5170

South Asian (SAS)

AF:

0.102

AC:

490

AN:

4822

European-Finnish (FIN)

AF:

0.125

AC:

1332

AN:

10620

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.137

AC:

9343

AN:

67982

Other (OTH)

AF:

0.179

AC:

377

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

991

1982

2974

3965

4956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<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:

0.142

Hom.:

6618

Bravo

AF:

0.154

Asia WGS

AF:

0.0900

AC:

315

AN:

3478

EpiCase

AF:

0.150

EpiControl

AF:

0.147

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Epidermolysis bullosa simplex (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.23

(source)

DANN

Benign

0.25

PhyloP100

-6.1

PromoterAI

0.043

Neutral

(source)

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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