Variant 1-37475795-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001323551.2(ZC3H12A):c.-608C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,612,496 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00064 ( 12 hom. )

Consequence

ZC3H12A
NM_001323551.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0670

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003866762).

BP6

Variant 1-37475795-C-T is Benign according to our data. Variant chr1-37475795-C-T is described in ClinVar as [Benign]. Clinvar id is 784945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00531 (808/152302) while in subpopulation AFR AF= 0.0183 (760/41566). AF 95% confidence interval is 0.0172. There are 9 homozygotes in gnomad4. There are 382 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H12A	NM_025079.3 linkuse as main transcript	c.299C>T	p.Pro100Leu	missense_variant	2/6	ENST00000373087.7	NP_079355.2	Q5D1E8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZC3H12A	ENST00000373087.7 linkuse as main transcript	c.299C>T	p.Pro100Leu	missense_variant	2/6	1	NM_025079.3	ENSP00000362179.5		Q5D1E8
ZC3H12A	ENST00000640233.1 linkuse as main transcript	n.299C>T		non_coding_transcript_exon_variant	2/6	5		ENSP00000492053.1		A0A1W2PQC8

Frequencies

GnomAD3 genomes

AF:

0.00530

AC:

806

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00179

AC:

445

AN:

248784

Hom.:

AF XY:

0.00130

AC XY:

176

AN XY:

134872

show subpopulations

Gnomad AFR exome

AF:

0.0174

Gnomad AMR exome

AF:

0.00447

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000446

Gnomad OTH exome

AF:

0.000988

GnomAD4 exome

AF:

0.000641

AC:

936

AN:

1460194

Hom.:

Cov.:

AF XY:

0.000536

AC XY:

389

AN XY:

726194

show subpopulations

Gnomad4 AFR exome

AF:

0.0192

Gnomad4 AMR exome

AF:

0.00403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.00134

GnomAD4 genome

AF:

0.00531

AC:

808

AN:

152302

Hom.:

Cov.:

AF XY:

0.00513

AC XY:

382

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0183

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000988

Hom.:

Bravo

AF:

0.00651

ESP6500AA

AF:

0.0186

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00199

AC:

242

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.13

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.8

REVEL

Benign

0.083

Sift

Benign

0.45

Sift4G

Benign

0.34

Polyphen

0.0020

Vest4

0.049

MVP

0.043

MPC

0.54

ClinPred

0.0021

GERP RS

2.2

Varity_R

0.023

gMVP

0.21

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