NM_025079.3:c.367C>T

Variant names:

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

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.367C>T​(p.Pro123Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000574 in 1,568,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: ZC3H12A NM_025079.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.483
• Publications: 2 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=0.030569136).

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.367C>T	p.Pro123Ser	missense	Exon 2 of 6	NP_079355.2	Q5D1E8
	ZC3H12A	NM_001323550.2		c.367C>T	p.Pro123Ser	missense	Exon 2 of 6	NP_001310479.1	Q5D1E8
	ZC3H12A	NM_001323551.2		c.-540C>T		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.367C>T	p.Pro123Ser	missense	Exon 2 of 6	ENSP00000362179.5	Q5D1E8
	ZC3H12A	ENST00000855881.1		c.367C>T	p.Pro123Ser	missense	Exon 2 of 6	ENSP00000525940.1
	ZC3H12A	ENST00000855882.1		c.367C>T	p.Pro123Ser	missense	Exon 2 of 6	ENSP00000525941.1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000473 AC: 10 AN: 211482 AF XY: 0.0000521

Gnomad AFR exome AF: 0.000134

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: 0.0000814

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000572 AC: 81 AN: 1416620 Hom.: 0 Cov.: 31 AF XY: 0.0000671 AC XY: 47 AN XY: 700330

African (AFR) AF: 0.00 AC: 0 AN: 31994

American (AMR) AF: 0.00 AC: 0 AN: 38804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23332

East Asian (EAS) AF: 0.00 AC: 0 AN: 39172

South Asian (SAS) AF: 0.00 AC: 0 AN: 81002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5542

European-Non Finnish (NFE) AF: 0.0000735 AC: 80 AN: 1089126

Other (OTH) AF: 0.0000172 AC: 1 AN: 58294

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74358

African (AFR) AF: 0.0000241 AC: 1 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000132 Hom.: 0

Bravo AF: 0.0000793

ESP6500AA AF: 0.000455 AC: 2

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.0000413 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	0.069
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.67
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.48
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.55	N
REVEL	Benign	0.015
Sift	Benign	1.0	T
Sift4G	Benign	0.95	T
Polyphen		0.015	B
Vest4		0.094
MVP		0.068
MPC		0.53
ClinPred		0.025	T
GERP RS		-0.11
Varity_R		0.022
gMVP		0.43
Mutation Taster		=94/6	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: rs147048541; hg19: chr1-37941464;