Variant 20-297974-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033089.7(ZCCHC3):c.388G>A(p.Ala130Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,305,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ZCCHC3
NM_033089.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.895

Variant links:

Genes affected

ZCCHC3 (HGNC:16230): (zinc finger CCHC-type containing 3) Enables double-stranded DNA binding activity. Involved in several processes, including cellular response to exogenous dsRNA; detection of virus; and positive regulation of RIG-I signaling pathway. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZCCHC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.08209553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZCCHC3	NM_033089.7 linkuse as main transcript	c.388G>A	p.Ala130Thr	missense_variant	1/1	ENST00000500893.4	NP_149080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZCCHC3	ENST00000500893.4 linkuse as main transcript	c.388G>A	p.Ala130Thr	missense_variant	1/1		NM_033089.7	ENSP00000484056	P1	Q9NUD5-1

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151642

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000113

AC:

131

AN:

1154316

Hom.:

Cov.:

AF XY:

0.000104

AC XY:

AN XY:

556712

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000134

Gnomad4 OTH exome

AF:

0.0000430

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151642

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74064

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.0000151

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

Sep 01, 2021

The c.388G>A (p.A130T) alteration is located in exon 1 (coding exon 1) of the ZCCHC3 gene. This alteration results from a G to A substitution at nucleotide position 388, causing the alanine (A) at amino acid position 130 to be replaced by a threonine (T). 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

0.098

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.018

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.47

M_CAP

Benign

0.074

MetaRNN

Benign

0.082

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.81

Sift4G

Benign

0.21

Polyphen

0.069

Vest4

0.15

MutPred

0.34

Gain of glycosylation at A130 (P = 0.0121);

MVP

0.28

ClinPred

0.18

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.95

Varity_R

0.017

gMVP

0.28

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