chr1-37475863-C-G

Variant names:

• chr1-37475863-C-G
• rs147048541
• NM_025079.3:c.367C>G

Variant summary

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

The NM_025079.3(ZC3H12A):​c.367C>G​(p.Pro123Ala) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P123S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZC3H12A NM_025079.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483

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=0.04896176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3H12A	NM_025079.3	c.367C>G	p.Pro123Ala	missense_variant	Exon 2 of 6	ENST00000373087.7	NP_079355.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3H12A	ENST00000373087.7	c.367C>G	p.Pro123Ala	missense_variant	Exon 2 of 6	1	NM_025079.3	ENSP00000362179.5
ZC3H12A	ENST00000640233.1	n.367C>G		non_coding_transcript_exon_variant	Exon 2 of 6	5		ENSP00000492053.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.56
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	M
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.014
Sift	Benign	0.66	T
Sift4G	Benign	0.61	T
Polyphen		0.0070	B
Vest4		0.18
MutPred		0.26		Loss of catalytic residue at P123 (P = 0.0039);
MVP		0.082
MPC		0.51
ClinPred		0.037	T
GERP RS		-0.11
Varity_R		0.024
gMVP		0.38

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: rs147048541; hg19: chr1-37941464;