Variant chr6-149451205-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207360.3(ZC3H12D):c.1062C>G(p.Asp354Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,310,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 8.6e-7 ( 0 hom. )

Consequence

ZC3H12D
NM_207360.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.451

Variant links:

Genes affected

ZC3H12D (HGNC:21175): (zinc finger CCCH-type containing 12D) Predicted to enable endoribonuclease activity and mRNA binding activity. Involved in negative regulation of G1/S transition of mitotic cell cycle and negative regulation of cell growth. Located in P-body and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZC3H12D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05015111).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC3H12D	NM_207360.3 linkuse as main transcript	c.1062C>G	p.Asp354Glu	missense_variant	6/6	ENST00000409806.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZC3H12D	ENST00000409806.8 linkuse as main transcript	c.1062C>G	p.Asp354Glu	missense_variant	6/6	1	NM_207360.3	P1	A2A288-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

8.64e-7

AC:

AN:

1158030

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

553716

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:

0.0000266

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151996

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Oct 22, 2021

The c.1062C>G (p.D354E) alteration is located in exon 6 (coding exon 5) of the ZC3H12D gene. This alteration results from a C to G substitution at nucleotide position 1062, causing the aspartic acid (D) at amino acid position 354 to be replaced by a glutamic acid (E). 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

0.11

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

9.9

DANN

Benign

0.90

DEOGEN2

Benign

0.0060

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.30

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.48

REVEL

Benign

0.024

Sift

Benign

0.14

Sift4G

Benign

0.97

Polyphen

0.12

Vest4

0.022

MutPred

0.15

Loss of sheet (P = 0.0817);

MVP

0.043

MPC

0.91

ClinPred

0.056

GERP RS

0.66

Varity_R

0.074

gMVP

0.083

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