Variant 16-11763610-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014153.4(ZC3H7A):c.1870C>T(p.Arg624Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000125 in 1,605,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZC3H7A
NM_014153.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.45

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.91

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H7A	NM_014153.4 linkuse as main transcript	c.1870C>T	p.Arg624Cys	missense_variant	16/23	ENST00000355758.9	NP_054872.2	Q8IWR0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZC3H7A	ENST00000355758.9 linkuse as main transcript	c.1870C>T	p.Arg624Cys	missense_variant	16/23	1	NM_014153.4	ENSP00000347999.4	Q8IWR0-1
ZC3H7A	ENST00000396516.6 linkuse as main transcript	c.1870C>T	p.Arg624Cys	missense_variant	15/22	1		ENSP00000379773.2	Q8IWR0-1
ZC3H7A	ENST00000571198.5 linkuse as main transcript	c.1600C>T	p.Arg534Cys	missense_variant	14/19	2		ENSP00000459747.1	I3L2K5
ZC3H7A	ENST00000571405.5 linkuse as main transcript	n.223C>T		non_coding_transcript_exon_variant	3/10	2		ENSP00000459811.1	I3L2N8

Frequencies

GnomAD3 genomes

AF:

0.00000664

AC:

AN:

150626

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000981

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455314

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723958

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:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000664

AC:

AN:

150626

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73422

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000981

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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 27, 2024

The c.1870C>T (p.R624C) alteration is located in exon 16 (coding exon 15) of the ZC3H7A gene. This alteration results from a C to T substitution at nucleotide position 1870, causing the arginine (R) at amino acid position 624 to be replaced by a cysteine (C). 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

Pathogenic

0.87

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.49

T;T;.

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

.;D;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.91

D;D;D

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.7

M;M;.

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-6.8

D;D;.

REVEL

Uncertain

0.53

Sift

Pathogenic

0.0

D;D;.

Sift4G

Pathogenic

0.0010

D;D;.

Polyphen

1.0

D;D;.

Vest4

0.93

MutPred

0.81

Loss of MoRF binding (P = 0.0286);Loss of MoRF binding (P = 0.0286);.;

MVP

0.40

MPC

1.7

ClinPred

1.0

GERP RS

5.3

Varity_R

0.76

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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