Genetic Variant ZC3H12A:p.Gln373* (chr1-37482928-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_025079.3(ZC3H12A):c.1117C>T(p.Gln373*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

ZC3H12A
NM_025079.3 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.21

Publications

2 publications found

Variant links:

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]

ZC3H12A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZC3H12A	NM_025079.3	MANE Select	c.1117C>T	p.Gln373*	stop_gained	Exon 6 of 6	NP_079355.2
ZC3H12A	NM_001323550.2		c.1117C>T	p.Gln373*	stop_gained	Exon 6 of 6	NP_001310479.1
ZC3H12A	NM_001323551.2		c.295C>T	p.Gln99*	stop_gained	Exon 6 of 6	NP_001310480.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZC3H12A	ENST00000373087.7	TSL:1 MANE Select	c.1117C>T	p.Gln373*	stop_gained	Exon 6 of 6	ENSP00000362179.5
ZC3H12A	ENST00000855881.1		c.1117C>T	p.Gln373*	stop_gained	Exon 6 of 6	ENSP00000525940.1
ZC3H12A	ENST00000855882.1		c.1117C>T	p.Gln373*	stop_gained	Exon 6 of 6	ENSP00000525941.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.017

FATHMM_MKL

Benign

0.73

PhyloP100

1.2

Vest4

0.73

GERP RS

4.2

Mutation Taster

=52/148

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.83

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.83

Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over