12-56124624-T-G

Variant names:

• chr12-56124624-T-G
• rs11171747
• NM_032786.3:c.*2757T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032786.3(ZC3H10):​c.*2757T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,188 control chromosomes in the GnomAD database, including 8,977 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 0.31 (8977 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZC3H10 NM_032786.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

Genes affected

ZC3H10 (HGNC:25893): (zinc finger CCCH-type containing 10) Enables miRNA binding activity. Involved in negative regulation of production of miRNAs involved in gene silencing by miRNA and posttranscriptional regulation of gene expression. Predicted to be active in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ESYT1 (HGNC:29534): (extended synaptotagmin 1) Enables identical protein binding activity. Predicted to be involved in endoplasmic reticulum-plasma membrane tethering and lipid transport. Located in endoplasmic reticulum. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258317 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3H10	NM_032786.3	c.*2757T>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000257940.7	NP_116175.1
ZC3H10	NM_001303124.2	c.*2757T>G		3_prime_UTR_variant	Exon 3 of 3		NP_001290053.1
ZC3H10	NM_001303125.2	c.*2757T>G		3_prime_UTR_variant	Exon 3 of 3		NP_001290054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3H10	ENST00000257940.7	c.*2757T>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_032786.3	ENSP00000257940.2
ESYT1	ENST00000551790.5	c.-143-3916T>G		intron_variant	Intron 2 of 5	4		ENSP00000447756.1
ENSG00000258317	ENST00000549438.1	n.337-2386A>C		intron_variant	Intron 1 of 2	3
ENSG00000258317	ENST00000550947.1	n.526+3895A>C		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47666 AN: 152070 Hom.: 8974 Cov.: 33

Gnomad AFR AF: 0.0926

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.370

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.313 AC: 47661 AN: 152188 Hom.: 8977 Cov.: 33 AF XY: 0.319 AC XY: 23707 AN XY: 74412

Gnomad4 AFR AF: 0.0923

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.367

Alfa AF: 0.382 Hom.: 24048

Bravo AF: 0.307

Asia WGS AF: 0.318 AC: 1105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.8
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs11171747; hg19: chr12-56518408;