1-37475768-C-G

Variant names:

• chr1-37475768-C-G
• rs747495424
• NM_025079.3:c.272C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025079.3(ZC3H12A):​c.272C>G​(p.Ala91Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: ZC3H12A NM_025079.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.672
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07706487).

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.272C>G	p.Ala91Gly	missense	Exon 2 of 6	NP_079355.2	Q5D1E8
	ZC3H12A	NM_001323550.2		c.272C>G	p.Ala91Gly	missense	Exon 2 of 6	NP_001310479.1	Q5D1E8
	ZC3H12A	NM_001323551.2		c.-635C>G		5_prime_UTR	Exon 2 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.272C>G	p.Ala91Gly	missense	Exon 2 of 6	ENSP00000362179.5	Q5D1E8
	ZC3H12A	ENST00000855881.1		c.272C>G	p.Ala91Gly	missense	Exon 2 of 6	ENSP00000525940.1
	ZC3H12A	ENST00000855882.1		c.272C>G	p.Ala91Gly	missense	Exon 2 of 6	ENSP00000525941.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 250156 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000532

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461300 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 726924

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111868

Other (OTH) AF: 0.0000331 AC: 2 AN: 60378

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.67
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.039
Sift	Benign	0.24	T
Sift4G	Benign	0.29	T
Polyphen		0.023	B
Vest4		0.099
MutPred		0.20		Loss of helix (P = 0.0444)
MVP		0.043
MPC		0.54
ClinPred		0.10	T
GERP RS		4.8
Varity_R		0.078
gMVP		0.18
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs747495424; hg19: chr1-37941369;