Variant 12-52839982-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_173352.4(KRT78):c.1050C>T(p.Asn350Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,611,784 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 3 hom. )

Consequence

KRT78
NM_173352.4 splice_region, synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.709

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 Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 12-52839982-G-A is Benign according to our data. Variant chr12-52839982-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3289540.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.709 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT78	NM_173352.4 linkuse as main transcript	c.1050C>T	p.Asn350Asn	splice_region_variant, synonymous_variant	7/9	ENST00000304620.5	NP_775487.2	Q8N1N4-1
KRT78	NM_001300814.1 linkuse as main transcript	c.720C>T	p.Asn240Asn	splice_region_variant, synonymous_variant	7/9		NP_001287743.1	Q8N1N4-2
KRT78	XM_011538010.2 linkuse as main transcript	c.954C>T	p.Asn318Asn	splice_region_variant, synonymous_variant	6/8		XP_011536312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT78	ENST00000304620.5 linkuse as main transcript	c.1050C>T	p.Asn350Asn	splice_region_variant, synonymous_variant	7/9	1	NM_173352.4	ENSP00000306261.4		Q8N1N4-1
KRT78	ENST00000359499.8 linkuse as main transcript	c.720C>T	p.Asn240Asn	splice_region_variant, synonymous_variant	7/9	1		ENSP00000352479.4		Q8N1N4-2

Frequencies

GnomAD3 genomes

AF:

0.000789

AC:

120

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00140

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000480

AC:

120

AN:

250242

Hom.:

AF XY:

0.000451

AC XY:

AN XY:

135318

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000955

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00135

AC:

1972

AN:

1459530

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

914

AN XY:

725830

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.00168

Gnomad4 OTH exome

AF:

0.00134

GnomAD4 genome

AF:

0.000788

AC:

120

AN:

152254

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00140

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.000714

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.00125

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

Mar 19, 2024

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

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.6

DANN

Benign

0.82

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