NM_015117.3:c.1562-500G>C

Variant names:

• chr8-143508399-C-G
• rs2980275
• NM_015117.3:c.1562-500G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015117.3(ZC3H3):​c.1562-500G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0376 in 152,300 control chromosomes in the GnomAD database, including 327 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.038 (327 hom., cov: 34)
• Consequence: ZC3H3 NM_015117.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978
• Publications: 1 publications found

Genes affected

ZC3H3 (HGNC:28972): (zinc finger CCCH-type containing 3) Predicted to enable SMAD binding activity. Involved in regulation of mRNA polyadenylation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015117.3. 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
	ZC3H3	NM_015117.3	MANE Select	c.1562-500G>C		intron	N/A	NP_055932.2	Q8IXZ2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H3	ENST00000262577.6	TSL:1 MANE Select	c.1562-500G>C		intron	N/A	ENSP00000262577.5	Q8IXZ2-1
	ZC3H3	ENST00000875766.1		c.1562-500G>C		intron	N/A	ENSP00000545825.1
	ZC3H3	ENST00000932295.1		c.1562-500G>C		intron	N/A	ENSP00000602354.1

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5701 AN: 152182 Hom.: 323 Cov.: 34

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0161

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0277

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0376 AC: 5722 AN: 152300 Hom.: 327 Cov.: 34 AF XY: 0.0375 AC XY: 2791 AN XY: 74468

African (AFR) AF: 0.130 AC: 5394 AN: 41546

American (AMR) AF: 0.0161 AC: 246 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68036

Other (OTH) AF: 0.0274 AC: 58 AN: 2116

Alfa AF: 0.00190 Hom.: 1

Bravo AF: 0.0435

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.58
PhyloP100		-0.98
Mutation Taster		=100/0	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: rs2980275; hg19: chr8-144590569;