1-37483451-G-A

Variant names:

• chr1-37483451-G-A
• rs17849897
• NM_025079.3:c.1640G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_025079.3(ZC3H12A):​c.1640G>A​(p.Gly547Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 1,614,016 control chromosomes in the GnomAD database, including 552 homozygotes. 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: 𝑓 0.019 (50 hom., cov: 33)
  • Exomes 𝑓: 0.024 (502 hom.)
• Consequence: ZC3H12A NM_025079.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020011067).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0192 (2923/152320) while in subpopulation NFE AF = 0.0263 (1789/68004). AF 95% confidence interval is 0.0253. There are 50 homozygotes in GnomAd4. There are 1475 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 50 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H12A	NM_025079.3	MANE Select	c.1640G>A	p.Gly547Asp	missense	Exon 6 of 6	NP_079355.2
	ZC3H12A	NM_001323550.2		c.1640G>A	p.Gly547Asp	missense	Exon 6 of 6	NP_001310479.1
	ZC3H12A	NM_001323551.2		c.818G>A	p.Gly273Asp	missense	Exon 6 of 6	NP_001310480.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H12A	ENST00000373087.7	TSL:1 MANE Select	c.1640G>A	p.Gly547Asp	missense	Exon 6 of 6	ENSP00000362179.5
	ZC3H12A	ENST00000855881.1		c.1640G>A	p.Gly547Asp	missense	Exon 6 of 6	ENSP00000525940.1
	ZC3H12A	ENST00000855882.1		c.1640G>A	p.Gly547Asp	missense	Exon 6 of 6	ENSP00000525941.1

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2923 AN: 152202 Hom.: 50 Cov.: 33

Gnomad AFR AF: 0.00519

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0482

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.0186

GnomAD2 exomes AF: 0.0201 AC: 5029 AN: 250756 AF XY: 0.0195

Gnomad AFR exome AF: 0.00438

Gnomad AMR exome AF: 0.0126

Gnomad ASJ exome AF: 0.00597

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0498

Gnomad NFE exome AF: 0.0285

Gnomad OTH exome AF: 0.0188

GnomAD4 exome AF: 0.0243 AC: 35473 AN: 1461696 Hom.: 502 Cov.: 32 AF XY: 0.0233 AC XY: 16943 AN XY: 727136

African (AFR) AF: 0.00391 AC: 131 AN: 33480

American (AMR) AF: 0.0135 AC: 605 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00601 AC: 157 AN: 26128

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

South Asian (SAS) AF: 0.00126 AC: 109 AN: 86254

European-Finnish (FIN) AF: 0.0459 AC: 2448 AN: 53316

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5766

European-Non Finnish (NFE) AF: 0.0278 AC: 30862 AN: 1111950

Other (OTH) AF: 0.0189 AC: 1141 AN: 60380

GnomAD4 genome AF: 0.0192 AC: 2923 AN: 152320 Hom.: 50 Cov.: 33 AF XY: 0.0198 AC XY: 1475 AN XY: 74480

African (AFR) AF: 0.00517 AC: 215 AN: 41584

American (AMR) AF: 0.0173 AC: 265 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.0482 AC: 512 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0263 AC: 1789 AN: 68004

Other (OTH) AF: 0.0184 AC: 39 AN: 2116

Alfa AF: 0.0248 Hom.: 40

Bravo AF: 0.0171

TwinsUK AF: 0.0259 AC: 96

ALSPAC AF: 0.0306 AC: 118

ESP6500AA AF: 0.00749 AC: 33

ESP6500EA AF: 0.0214 AC: 184

ExAC AF: 0.0211 AC: 2562

Asia WGS AF: 0.00231 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.7
DANN	Benign	0.25
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.4
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.10
Sift	Benign	0.88	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.012
MPC		0.68
ClinPred		0.0032	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.032
gMVP		0.32
Mutation Taster		=94/6	polymorphism (auto)

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: rs17849897; hg19: chr1-37949052;