Variant 16-11756278-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014153.4(ZC3H7A):c.2521G>A(p.Gly841Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZC3H7A
NM_014153.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.95

Variant links:

Genes affected

ZC3H7A (HGNC:30959): (zinc finger CCCH-type containing 7A) Enables miRNA binding activity. Involved in production of miRNAs involved in gene silencing by miRNA. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZC3H7A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H7A	NM_014153.4 linkuse as main transcript	c.2521G>A	p.Gly841Arg	missense_variant	21/23	ENST00000355758.9	NP_054872.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZC3H7A	ENST00000355758.9 linkuse as main transcript	c.2521G>A	p.Gly841Arg	missense_variant	21/23	1	NM_014153.4	ENSP00000347999	P1	Q8IWR0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251392

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461778

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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 06, 2021

The c.2521G>A (p.G841R) alteration is located in exon 21 (coding exon 20) of the ZC3H7A gene. This alteration results from a G to A substitution at nucleotide position 2521, causing the glycine (G) at amino acid position 841 to be replaced by an arginine (R). 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

Uncertain

0.46

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.018

T;T;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;D;D

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.7

L;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.91

N;N;.

REVEL

Benign

0.19

Sift

Benign

0.063

T;T;.

Sift4G

Benign

0.066

T;T;D

Polyphen

1.0

D;D;.

Vest4

0.64

MutPred

0.30

Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);.;

MVP

0.043

MPC

1.6

ClinPred

0.85

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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