Variant 17-40863210-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000223.4(KRT12):c.1229T>G(p.Val410Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000201 in 1,614,054 control chromosomes in the GnomAD database, including 1 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 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

KRT12
NM_000223.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.160

Variant links:

Genes affected

KRT12 (HGNC:6414): (keratin 12) KRT12 encodes the type I intermediate filament chain keratin 12, expressed in corneal epithelia. Mutations in this gene lead to Meesmann corneal dystrophy. [provided by RefSeq, Jul 2008]

KRT12 links:

ENSG00000265359 (HGNC:):

ENSG00000265359 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004383743).

BP6

Variant 17-40863210-A-C is Benign according to our data. Variant chr17-40863210-A-C is described in ClinVar as [Benign]. Clinvar id is 2716869.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000322 (49/152356) while in subpopulation EAS AF= 0.0056 (29/5180). AF 95% confidence interval is 0.004. There are 0 homozygotes in gnomad4. There are 32 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 49 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT12	NM_000223.4 linkuse as main transcript	c.1229T>G	p.Val410Gly	missense_variant	6/8	ENST00000251643.5	NP_000214.1	Q99456
LOC105371777	XR_934754.3 linkuse as main transcript	n.63+12350A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KRT12	ENST00000251643.5 linkuse as main transcript	c.1229T>G	p.Val410Gly	missense_variant	6/8	1	NM_000223.4	ENSP00000251643.4	Q99456
ENSG00000265359	ENST00000579136.1 linkuse as main transcript	n.186A>C		non_coding_transcript_exon_variant	2/2	3
KRT12	ENST00000648535.1 linkuse as main transcript	n.521T>G		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00559

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000530

AC:

132

AN:

249266

Hom.:

AF XY:

0.000547

AC XY:

AN XY:

135220

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00534

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.0000445

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000188

AC:

275

AN:

1461698

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

148

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00408

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00137

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000322

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.000429

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00560

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000320

Hom.:

Bravo

AF:

0.000246

ExAC

AF:

0.000585

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.37

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.10

.;T

M_CAP

Benign

0.046

MetaRNN

Benign

0.0044

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.63

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.73

.;N

REVEL

Benign

0.27

Sift

Benign

0.35

.;T

Sift4G

Benign

0.35

.;T

Polyphen

0.0050

B;B

Vest4

0.15

MVP

0.72

MPC

1.2

ClinPred

0.0069

GERP RS

0.71

Varity_R

0.077

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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