rs8743

Positions:

• chr16-11758498-A-C
• chr16-11758498-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000355758.9(ZC3H7A):​c.2361T>G​(p.Val787=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,611,116 control chromosomes in the GnomAD database, including 154,964 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 0.48 (18096 hom., cov: 32)
  • Exomes 𝑓: 0.43 (136868 hom.)
• Consequence: ZC3H7A ENST00000355758.9 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

Genes affected

ZC3H7A (HGNC:30959): (zinc finger CCCH-type containing 7A) Enables miRNA binding activity. Involved in production of miRNAs involved in gene silencing by miRNA. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=1.75 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H7A	NM_014153.4	c.2361T>G	p.Val787=	synonymous_variant	20/23	ENST00000355758.9	NP_054872.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZC3H7A	ENST00000355758.9	c.2361T>G	p.Val787=	synonymous_variant	20/23	1	NM_014153.4	ENSP00000347999	P1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72735 AN: 151884 Hom.: 18085 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.469

GnomAD3 exomes AF: 0.452 AC: 113564 AN: 251124 Hom.: 26741 AF XY: 0.439 AC XY: 59552 AN XY: 135766

Gnomad AFR exome AF: 0.602

Gnomad AMR exome AF: 0.569

Gnomad ASJ exome AF: 0.369

Gnomad EAS exome AF: 0.616

Gnomad SAS exome AF: 0.399

Gnomad FIN exome AF: 0.369

Gnomad NFE exome AF: 0.407

Gnomad OTH exome AF: 0.441

GnomAD4 exome AF: 0.429 AC: 625743 AN: 1459114 Hom.: 136868 Cov.: 37 AF XY: 0.426 AC XY: 309199 AN XY: 726010

Gnomad4 AFR exome AF: 0.606

Gnomad4 AMR exome AF: 0.561

Gnomad4 ASJ exome AF: 0.371

Gnomad4 EAS exome AF: 0.581

Gnomad4 SAS exome AF: 0.393

Gnomad4 FIN exome AF: 0.374

Gnomad4 NFE exome AF: 0.418

Gnomad4 OTH exome AF: 0.454

GnomAD4 genome AF: 0.479 AC: 72779 AN: 152002 Hom.: 18096 Cov.: 32 AF XY: 0.477 AC XY: 35447 AN XY: 74308

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.465

Alfa AF: 0.438 Hom.: 10281

Bravo AF: 0.501

Asia WGS AF: 0.503 AC: 1748 AN: 3478

EpiCase AF: 0.414

EpiControl AF: 0.409

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.0
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs8743; hg19: chr16-11852354; COSMIC: COSV63268503; COSMIC: COSV63268503;