Variant 12-52839471-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_173352.4(KRT78):c.1285A>C(p.Thr429Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,451,618 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

KRT78
NM_173352.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.61

Variant links:

Genes affected

KRT78 (HGNC:28926): (keratin 78) This gene is a member of the type II keratin gene family and encodes a protein with an intermediate filament domain. Keratins are the major structural proteins in epithelial cells, forming a cytoplasmic network of 10 to 12 nm wide intermediate filaments and creating a scaffold that gives cells the ability to withstand mechanical and non-mechanical stresses. The genes of the type II keratin family are located as a gene cluster at 12p13.13. Four pseudogenes of this gene family have been identified. [provided by RefSeq, Jul 2008]

KRT78 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020130396).

BP6

Variant 12-52839471-T-G is Benign according to our data. Variant chr12-52839471-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2303411.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT78	NM_173352.4 linkuse as main transcript	c.1285A>C	p.Thr429Pro	missense_variant	8/9	ENST00000304620.5	NP_775487.2	Q8N1N4-1
KRT78	NM_001300814.1 linkuse as main transcript	c.955A>C	p.Thr319Pro	missense_variant	8/9		NP_001287743.1	Q8N1N4-2
KRT78	XM_011538010.2 linkuse as main transcript	c.1189A>C	p.Thr397Pro	missense_variant	7/8		XP_011536312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KRT78	ENST00000304620.5 linkuse as main transcript	c.1285A>C	p.Thr429Pro	missense_variant	8/9	1	NM_173352.4	ENSP00000306261.4	Q8N1N4-1
KRT78	ENST00000359499.8 linkuse as main transcript	c.955A>C	p.Thr319Pro	missense_variant	8/9	1		ENSP00000352479.4	Q8N1N4-2
KRT78	ENST00000547920.1 linkuse as main transcript	c.51-99A>C		intron_variant		3		ENSP00000448562.2	H0YI54

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000865

AC:

AN:

231206

Hom.:

AF XY:

0.0000160

AC XY:

AN XY:

124750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000709

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1451618

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

721230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000474

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.8

DANN

Benign

0.75

DEOGEN2

Benign

0.000098

.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.033

T;T

M_CAP

Benign

0.063

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

-0.64

.;N

PrimateAI

Benign

0.22

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.14

Sift

Benign

1.0

T;T

Sift4G

Benign

0.89

T;T

Polyphen

0.0

.;B

Vest4

0.073

MutPred

0.31

.;Loss of helix (P = 0.0033);

MVP

0.22

MPC

0.046

ClinPred

0.054

GERP RS

-3.6

Varity_R

0.099

gMVP

0.072

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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