Variant 1-37481735-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_025079.3(ZC3H12A):c.718G>A(p.Val240Met) variant causes a missense change. The variant allele was found at a frequency of 0.000963 in 1,614,240 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts 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 0.0034 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00071 ( 2 hom. )

Consequence

ZC3H12A
NM_025079.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.38

Variant links:

Genes affected

ZC3H12A (HGNC:26259): (zinc finger CCCH-type containing 12A) ZC3H12A is an MCP1 (CCL2; MIM 158105)-induced protein that acts as a transcriptional activator and causes cell death of cardiomyocytes, possibly via induction of genes associated with apoptosis.[supplied by OMIM, Mar 2008]

ZC3H12A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010192007).

BP6

Variant 1-37481735-G-A is Benign according to our data. Variant chr1-37481735-G-A is described in ClinVar as [Benign]. Clinvar id is 709686.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC3H12A	NM_025079.3 linkuse as main transcript	c.718G>A	p.Val240Met	missense_variant	4/6	ENST00000373087.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZC3H12A	ENST00000373087.7 linkuse as main transcript	c.718G>A	p.Val240Met	missense_variant	4/6	1	NM_025079.3	P1
ZC3H12A	ENST00000471012.1 linkuse as main transcript	c.46G>A	p.Val16Met	missense_variant	1/2	3
ZC3H12A	ENST00000472312.1 linkuse as main transcript	n.566G>A		non_coding_transcript_exon_variant	2/2	2
ZC3H12A	ENST00000640233.1 linkuse as main transcript	c.718G>A	p.Val240Met	missense_variant, NMD_transcript_variant	4/6	5

Frequencies

GnomAD3 genomes

AF:

0.00340

AC:

517

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00905

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00615

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00127

AC:

320

AN:

251484

Hom.:

AF XY:

0.00113

AC XY:

154

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00935

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000448

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.000710

AC:

1038

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000707

AC XY:

514

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00935

Gnomad4 AMR exome

AF:

0.00279

Gnomad4 ASJ exome

AF:

0.00168

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000381

Gnomad4 OTH exome

AF:

0.00184

GnomAD4 genome

AF:

0.00339

AC:

517

AN:

152350

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

227

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00902

Gnomad4 AMR

AF:

0.00614

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00106

Hom.:

Bravo

AF:

0.00422

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00148

AC:

180

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000474

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

Invitae

Apr 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.060

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.24

T;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.89

D;D

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.3

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.2

N;.

REVEL

Benign

0.21

Sift

Uncertain

0.0010

D;.

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

D;.

Vest4

0.47

MVP

0.44

MPC

1.2

ClinPred

0.031

GERP RS

4.7

Varity_R

0.44

gMVP

0.74

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