chr1-37482964-G-A

Variant names:

• chr1-37482964-G-A
• rs201901997
• NM_025079.3:c.1153G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025079.3(ZC3H12A):​c.1153G>A​(p.Ala385Thr) 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. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A385G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZC3H12A NM_025079.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047700375).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025079.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H12A	NM_025079.3	MANE Select	c.1153G>A	p.Ala385Thr	missense	Exon 6 of 6	NP_079355.2	Q5D1E8
	ZC3H12A	NM_001323550.2		c.1153G>A	p.Ala385Thr	missense	Exon 6 of 6	NP_001310479.1	Q5D1E8
	ZC3H12A	NM_001323551.2		c.331G>A	p.Ala111Thr	missense	Exon 6 of 6	NP_001310480.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H12A	ENST00000373087.7	TSL:1 MANE Select	c.1153G>A	p.Ala385Thr	missense	Exon 6 of 6	ENSP00000362179.5	Q5D1E8
	ZC3H12A	ENST00000855881.1		c.1153G>A	p.Ala385Thr	missense	Exon 6 of 6	ENSP00000525940.1
	ZC3H12A	ENST00000855882.1		c.1153G>A	p.Ala385Thr	missense	Exon 6 of 6	ENSP00000525941.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	10
DANN	Benign	0.97
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.6
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.092
Sift	Benign	0.044	D
Sift4G	Benign	0.14	T
Polyphen		0.085	B
Vest4		0.023
MutPred		0.14		Gain of phosphorylation at A385 (P = 0.0447)
MVP		0.12
MPC		0.60
ClinPred		0.088	T
GERP RS		1.9
Varity_R		0.047
gMVP		0.21
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs201901997; hg19: chr1-37948565;