12-56120632-G-A

Position:

chr12-56120632-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032786.3(ZC3H10):c.70G>A(p.Glu24Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000437 in 1,603,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

ZC3H10
NM_032786.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.61

Variant links:

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]

ZC3H10 links:

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]

ESYT1 links:

ENSG00000258317 (HGNC:):

ENSG00000258317 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14794841).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H10	NM_032786.3 linkuse as main transcript	c.70G>A	p.Glu24Lys	missense_variant	3/3	ENST00000257940.7	NP_116175.1	Q96K80
ZC3H10	NM_001303124.2 linkuse as main transcript	c.70G>A	p.Glu24Lys	missense_variant	3/3		NP_001290053.1	Q96K80
ZC3H10	NM_001303125.2 linkuse as main transcript	c.70G>A	p.Glu24Lys	missense_variant	3/3		NP_001290054.1	Q96K80

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZC3H10	ENST00000257940.7 linkuse as main transcript	c.70G>A	p.Glu24Lys	missense_variant	3/3	1	NM_032786.3	ENSP00000257940.2		Q96K80

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000411

AC:

AN:

243026

Hom.:

AF XY:

0.00000763

AC XY:

AN XY:

131066

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000909

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1450988

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

720488

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.70G>A (p.E24K) alteration is located in exon 3 (coding exon 1) of the ZC3H10 gene. This alteration results from a G to A substitution at nucleotide position 70, causing the glutamic acid (E) at amino acid position 24 to be replaced by a lysine (K). 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

0.17

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

T;T;.;.

Eigen

Benign

0.031

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

T;T;T;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

N;.;.;.

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.55

N;N;N;N

REVEL

Benign

0.041

Sift

Benign

0.18

T;T;.;T

Sift4G

Benign

0.87

T;T;D;T

Polyphen

0.36

B;.;.;.

Vest4

0.25

MutPred

0.19

Gain of ubiquitination at E24 (P = 0.0066);Gain of ubiquitination at E24 (P = 0.0066);Gain of ubiquitination at E24 (P = 0.0066);Gain of ubiquitination at E24 (P = 0.0066);

MVP

0.068

MPC

1.2

ClinPred

0.30

GERP RS

4.8

Varity_R

0.17

gMVP

0.65

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over