Variant 1-37483451-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000373087.7(ZC3H12A):c.1640G>A(p.Gly547Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 1,614,016 control chromosomes in the GnomAD database, including 552 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.019 ( 50 hom., cov: 33)

Exomes 𝑓: 0.024 ( 502 hom. )

Consequence

ZC3H12A
ENST00000373087.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020011067).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0192 (2923/152320) while in subpopulation NFE AF= 0.0263 (1789/68004). AF 95% confidence interval is 0.0253. There are 50 homozygotes in gnomad4. There are 1475 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H12A	NM_025079.3 linkuse as main transcript	c.1640G>A	p.Gly547Asp	missense_variant	6/6	ENST00000373087.7	NP_079355.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZC3H12A	ENST00000373087.7 linkuse as main transcript	c.1640G>A	p.Gly547Asp	missense_variant	6/6	1	NM_025079.3	ENSP00000362179	P1
ZC3H12A	ENST00000640233.1 linkuse as main transcript	c.*872G>A		3_prime_UTR_variant, NMD_transcript_variant	6/6	5		ENSP00000492053

Frequencies

GnomAD3 genomes

AF:

0.0192

AC:

2923

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00519

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0173

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0482

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0263

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.0201

AC:

5029

AN:

250756

Hom.:

AF XY:

0.0195

AC XY:

2649

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.00438

Gnomad AMR exome

AF:

0.0126

Gnomad ASJ exome

AF:

0.00597

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00137

Gnomad FIN exome

AF:

0.0498

Gnomad NFE exome

AF:

0.0285

Gnomad OTH exome

AF:

0.0188

GnomAD4 exome

AF:

0.0243

AC:

35473

AN:

1461696

Hom.:

502

Cov.:

AF XY:

0.0233

AC XY:

16943

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00391

Gnomad4 AMR exome

AF:

0.0135

Gnomad4 ASJ exome

AF:

0.00601

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00126

Gnomad4 FIN exome

AF:

0.0459

Gnomad4 NFE exome

AF:

0.0278

Gnomad4 OTH exome

AF:

0.0189

GnomAD4 genome

AF:

0.0192

AC:

2923

AN:

152320

Hom.:

Cov.:

AF XY:

0.0198

AC XY:

1475

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00517

Gnomad4 AMR

AF:

0.0173

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0482

Gnomad4 NFE

AF:

0.0263

Gnomad4 OTH

AF:

0.0184

Alfa

AF:

0.0218

Hom.:

Bravo

AF:

0.0171

TwinsUK

AF:

0.0259

AC:

ALSPAC

AF:

0.0306

AC:

118

ESP6500AA

AF:

0.00749

AC:

ESP6500EA

AF:

0.0214

AC:

184

ExAC

AF:

0.0211

AC:

2562

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.74

CADD

Benign

9.7

DANN

Benign

0.25

DEOGEN2

Benign

0.023

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

0.42

REVEL

Benign

0.10

Sift

Benign

0.88

Sift4G

Benign

0.67

Polyphen

0.0

Vest4

0.012

MPC

0.68

ClinPred

0.0032

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.032

gMVP

0.32

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over