rs34031609

chr1-37482928-C-Gchr1-37482928-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025079.3(ZC3H12A):c.1117C>G(p.Gln373Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZC3H12A NM_025079.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.032309324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC3H12A	NM_025079.3	c.1117C>G	p.Gln373Glu	missense_variant	6/6	ENST00000373087.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZC3H12A	ENST00000373087.7	c.1117C>G	p.Gln373Glu	missense_variant	6/6	1	NM_025079.3	P1
ZC3H12A	ENST00000640233.1	c.*349C>G		3_prime_UTR_variant, NMD_transcript_variant	6/6	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	12
Dann	Benign	0.41
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.067
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.21		Gain of sheet (P = 0.1208);
MVP		0.19
MPC		0.59
ClinPred		0.074	T
GERP RS		4.2
Varity_R		0.059
gMVP		0.23

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

Other links and lift over

dbSNP: rs34031609; hg19: chr1-37948529;