12-52173719-C-T

Position:

chr12-52173719-C-T

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KRT80	NM_182507.3 linkuse as main transcript	c.712G>A	p.Val238Ile	missense_variant	5/9	ENST00000394815.3	NP_872313.2
KRT80	NM_001081492.2 linkuse as main transcript	c.712G>A	p.Val238Ile	missense_variant	5/9		NP_001074961.1
KRT80	XM_005268676.4 linkuse as main transcript	c.817G>A	p.Val273Ile	missense_variant	3/7		XP_005268733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT80	ENST00000394815.3 linkuse as main transcript	c.712G>A	p.Val238Ile	missense_variant	5/9	1	NM_182507.3	ENSP00000378292	P1	Q6KB66-1
KRT80	ENST00000313234.9 linkuse as main transcript	c.712G>A	p.Val238Ile	missense_variant	5/9	1		ENSP00000369361		Q6KB66-2
LINC00592	ENST00000640420.1 linkuse as main transcript	n.413+8768C>T		intron_variant, non_coding_transcript_variant		5
KRT80	ENST00000466011.1 linkuse as main transcript	n.868G>A		non_coding_transcript_exon_variant	3/7	2

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

GnomAD3 exomes

AF:

0.00361

AC:

901

AN:

249318

Hom.:

AF XY:

0.00266

AC XY:

360

AN XY:

135096

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 SAS exome

AF:

0.00101

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

Gnomad4 AFR exome

AF:

0.0460

Gnomad4 AMR exome

AF:

0.00203

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000684

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000728

Gnomad4 OTH exome

AF:

0.00278

GnomAD4 genome

AF:

0.0127

AC:

1932

AN:

152318

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

919

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0438

Gnomad4 AMR

AF:

0.00457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00183

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.18

.;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.55

T;T

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.33

N;N

REVEL

Benign

0.26

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.051

T;D

Polyphen

0.81

P;P

Vest4

0.41

MVP

0.44

MPC

0.089

ClinPred

0.0066

GERP RS

0.032

Varity_R

0.10

gMVP

0.067

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over