rs35725856

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_182507.3(KRT80):c.712G>A(p.Val238Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,612,312 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 41 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 35 hom. )

Consequence

KRT80
NM_182507.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.841

Publications

5 publications found

Variant links:

Genes affected

KRT80 (HGNC:27056): (keratin 80) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene's expression profile shows that it encodes a type II epithelial keratin, although structurally the encoded protein is more like a type II hair keratin. This protein is involved in cell differentiation, localizing near desmosomal plaques in earlier stages of differentiation but then dispersing throughout the cytoplasm in terminally differentiating cells. The type II keratins are clustered in a region of chromosome 12q13. Two transcript variants encoding two different fully functional isoforms have been found for this gene.[provided by RefSeq, Oct 2010]

KRT80 links:

LINC00592 (HGNC:27474): (long intergenic non-protein coding RNA 592)

LINC00592 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028851032).

BP6

Variant 12-52173719-C-T is Benign according to our data. Variant chr12-52173719-C-T is described in ClinVar as Benign. ClinVar VariationId is 785407.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0127 (1932/152318) while in subpopulation AFR AF = 0.0438 (1822/41558). AF 95% confidence interval is 0.0422. There are 41 homozygotes in GnomAd4. There are 919 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 41 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182507.3. 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
	KRT80	NM_182507.3	MANE Select	c.712G>A	p.Val238Ile	missense	Exon 5 of 9	NP_872313.2	Q6KB66-1
	KRT80	NM_001081492.2		c.712G>A	p.Val238Ile	missense	Exon 5 of 9	NP_001074961.1	Q6KB66-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRT80	ENST00000394815.3	TSL:1 MANE Select	c.712G>A	p.Val238Ile	missense	Exon 5 of 9	ENSP00000378292.2	Q6KB66-1
KRT80	ENST00000313234.9	TSL:1	c.712G>A	p.Val238Ile	missense	Exon 5 of 9	ENSP00000369361.2	Q6KB66-2
KRT80	ENST00000466011.1	TSL:2	n.868G>A		non_coding_transcript_exon	Exon 3 of 7

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1931

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0439

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00860

GnomAD2 exomes

AF:

0.00361

AC:

901

AN:

249318

AF XY:

0.00266

show subpopulations

Gnomad AFR exome

AF:

0.0490

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00134

AC:

1956

AN:

1459994

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

860

AN XY:

726440

show subpopulations

African (AFR)

AF:

0.0460

AC:

1541

AN:

33480

American (AMR)

AF:

0.00203

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.000684

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51564

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000728

AC:

AN:

1111984

Other (OTH)

AF:

0.00278

AC:

168

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

110

220

330

440

550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.0127

AC:

1932

AN:

152318

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

919

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0438

AC:

1822

AN:

41558

American (AMR)

AF:

0.00457

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68030

Other (OTH)

AF:

0.00851

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

101

201

302

402

503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00249

Hom.:

Bravo

AF:

0.0156

ESP6500AA

AF:

0.0452

AC:

199

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00463

AC:

562

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.18

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0029

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.4

PhyloP100

0.84

PrimateAI

Benign

0.31

PROVEAN

Benign

0.33

REVEL

Benign

0.26

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.051

Polyphen

0.81

Vest4

0.41

MVP

0.44

MPC

0.089

ClinPred

0.0066

GERP RS

0.032

Varity_R

0.10

gMVP

0.067

Mutation Taster

=96/4

polymorphism

(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