rs8743

Variant names:

• chr16-11758498-A-C
• rs8743
• NM_014153.4:c.2361T>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014153.4(ZC3H7A):​c.2361T>G​(p.Val787Val) 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 NM_014153.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 19 publications found

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]

TXNDC11-AS1 (HGNC:56375): (TXNDC11 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014153.4. 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
	ZC3H7A	NM_014153.4	MANE Select	c.2361T>G	p.Val787Val	synonymous	Exon 20 of 23	NP_054872.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H7A	ENST00000355758.9	TSL:1 MANE Select	c.2361T>G	p.Val787Val	synonymous	Exon 20 of 23	ENSP00000347999.4
	ZC3H7A	ENST00000396516.6	TSL:1	c.2361T>G	p.Val787Val	synonymous	Exon 19 of 22	ENSP00000379773.2
	ZC3H7A	ENST00000575984.1	TSL:1	c.-52T>G		5_prime_UTR	Exon 1 of 4	ENSP00000459477.1

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

GnomAD2 exomes AF: 0.452 AC: 113564 AN: 251124 AF XY: 0.439

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 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

African (AFR) AF: 0.606 AC: 20249 AN: 33420

American (AMR) AF: 0.561 AC: 25086 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 9696 AN: 26108

East Asian (EAS) AF: 0.581 AC: 23050 AN: 39672

South Asian (SAS) AF: 0.393 AC: 33900 AN: 86182

European-Finnish (FIN) AF: 0.374 AC: 19935 AN: 53302

Middle Eastern (MID) AF: 0.384 AC: 2214 AN: 5768

European-Non Finnish (NFE) AF: 0.418 AC: 464253 AN: 1109676

Other (OTH) AF: 0.454 AC: 27360 AN: 60308

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

African (AFR) AF: 0.599 AC: 24813 AN: 41438

American (AMR) AF: 0.544 AC: 8307 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1314 AN: 3470

East Asian (EAS) AF: 0.601 AC: 3102 AN: 5164

South Asian (SAS) AF: 0.397 AC: 1915 AN: 4818

European-Finnish (FIN) AF: 0.369 AC: 3902 AN: 10578

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27981 AN: 67942

Other (OTH) AF: 0.465 AC: 980 AN: 2108

Alfa AF: 0.439 Hom.: 13617

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.0
DANN	Benign	0.92
PhyloP100		1.7
Mutation Taster		=295/5	polymorphism (auto)

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

Other links and lift over

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