12-56121077-G-T

Position:

• chr12-56121077-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032786.3(ZC3H10):​c.515G>T​(p.Gly172Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZC3H10 NM_032786.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.24

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12434611).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H10	NM_032786.3	c.515G>T	p.Gly172Val	missense_variant	3/3	ENST00000257940.7	NP_116175.1
ZC3H10	NM_001303124.2	c.515G>T	p.Gly172Val	missense_variant	3/3		NP_001290053.1
ZC3H10	NM_001303125.2	c.515G>T	p.Gly172Val	missense_variant	3/3		NP_001290054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZC3H10	ENST00000257940.7	c.515G>T	p.Gly172Val	missense_variant	3/3	1	NM_032786.3	ENSP00000257940.2
ESYT1	ENST00000551790.5	c.-144+1926G>T		intron_variant		4		ENSP00000447756.1
ENSG00000258317	ENST00000549438.1	n.536-41C>A		intron_variant		3
ENSG00000258317	ENST00000550947.1	n.527-1012C>A		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.515G>T (p.G172V) alteration is located in exon 3 (coding exon 1) of the ZC3H10 gene. This alteration results from a G to T substitution at nucleotide position 515, causing the glycine (G) at amino acid position 172 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.026	T
Eigen	Benign	0.077
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.90	N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.15
Sift	Benign	0.44	T
Sift4G	Benign	0.36	T
Polyphen		0.97	D
Vest4		0.28
MutPred		0.19		Loss of relative solvent accessibility (P = 0.0404);
MVP		0.068
MPC		0.95
ClinPred		0.56	D
GERP RS		4.0
Varity_R		0.11
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-56514861;