12-56124624-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 45 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032786.3. 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
	ZC3H10	NM_032786.3	MANE Select	c.*2757T>G		3_prime_UTR	Exon 3 of 3	NP_116175.1	Q96K80
	ZC3H10	NM_001303124.2		c.*2757T>G		3_prime_UTR	Exon 3 of 3	NP_001290053.1	Q96K80
	ZC3H10	NM_001303125.2		c.*2757T>G		3_prime_UTR	Exon 3 of 3	NP_001290054.1	Q96K80

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H10	ENST00000257940.7	TSL:1 MANE Select	c.*2757T>G		3_prime_UTR	Exon 3 of 3	ENSP00000257940.2	Q96K80
	ESYT1	ENST00000551790.5	TSL:4	c.-143-3916T>G		intron	N/A	ENSP00000447756.1	F8VZB1
	ENSG00000258317	ENST00000549438.1	TSL:3	n.337-2386A>C		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0923 AC: 3835 AN: 41552

American (AMR) AF: 0.425 AC: 6492 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1243 AN: 3468

East Asian (EAS) AF: 0.441 AC: 2283 AN: 5176

South Asian (SAS) AF: 0.297 AC: 1432 AN: 4822

European-Finnish (FIN) AF: 0.437 AC: 4615 AN: 10572

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26581 AN: 67994

Other (OTH) AF: 0.367 AC: 776 AN: 2114

Alfa AF: 0.364 Hom.: 32139

Bravo AF: 0.307

Asia WGS AF: 0.318 AC: 1105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.8
DANN	Benign	0.82
PhyloP100		2.1

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: rs11171747; hg19: chr12-56518408;