NM_015117.3:c.1716-8150T>C

Variant names:

• chr8-143483735-A-G
• rs380904
• NM_015117.3:c.1716-8150T>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.1716-8150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,120 control chromosomes in the GnomAD database, including 40,118 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 0.73 (40118 hom., cov: 34)
• Consequence: ZC3H3 NM_015117.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488
• Publications: 16 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.784 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H3	NM_015117.3	MANE Select	c.1716-8150T>C		intron	N/A	NP_055932.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H3	ENST00000262577.6	TSL:1 MANE Select	c.1716-8150T>C		intron	N/A	ENSP00000262577.5

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110338 AN: 152002 Hom.: 40095 Cov.: 34

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.726 AC: 110412 AN: 152120 Hom.: 40118 Cov.: 34 AF XY: 0.732 AC XY: 54430 AN XY: 74356

African (AFR) AF: 0.697 AC: 28925 AN: 41502

American (AMR) AF: 0.736 AC: 11252 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2785 AN: 3470

East Asian (EAS) AF: 0.748 AC: 3857 AN: 5156

South Asian (SAS) AF: 0.805 AC: 3884 AN: 4826

European-Finnish (FIN) AF: 0.774 AC: 8199 AN: 10596

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49104 AN: 67958

Other (OTH) AF: 0.729 AC: 1542 AN: 2114

Alfa AF: 0.727 Hom.: 148867

Bravo AF: 0.719

Asia WGS AF: 0.783 AC: 2724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.52
PhyloP100		-0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs380904; hg19: chr8-144565905;