Variant 12-71611803-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4BS2_Supporting

The NM_144982.5(ZFC3H1):c.5712C>G(p.Cys1904Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000348 in 1,608,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

ZFC3H1
NM_144982.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.81

Variant links:

Genes affected

ZFC3H1 (HGNC:28328): (zinc finger C3H1-type containing) Predicted to enable metal ion binding activity. Predicted to be involved in RNA processing. Located in nucleus. Part of exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

ZFC3H1 links:

ZFC3H1 (HGNC:):

ZFC3H1 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=0.33730096).

BS2

High AC in GnomAd4 at 7 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFC3H1	NM_144982.5 linkuse as main transcript	c.5712C>G	p.Cys1904Trp	missense_variant	32/35	ENST00000378743.9	NP_659419.3	O60293-1
ZFC3H1	XM_047428485.1 linkuse as main transcript	c.4533C>G	p.Cys1511Trp	missense_variant	32/35		XP_047284441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZFC3H1	ENST00000378743.9 linkuse as main transcript	c.5712C>G	p.Cys1904Trp	missense_variant	32/35	1	NM_144982.5	ENSP00000368017.4	O60293-1
ZFC3H1	ENST00000552994.5 linkuse as main transcript	n.5712C>G		non_coding_transcript_exon_variant	32/34	1		ENSP00000446995.1	O60293-2
ZFC3H1	ENST00000551487.1 linkuse as main transcript	n.499C>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0000462

AC:

AN:

151470

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000396

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:

0.000101

AC:

AN:

247326

Hom.:

AF XY:

0.0000447

AC XY:

AN XY:

134300

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000616

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:

0.0000267

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000336

AC:

AN:

1456478

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

724696

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000540

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:

0.0000189

Gnomad4 OTH exome

AF:

0.0000666

GnomAD4 genome

AF:

0.0000462

AC:

AN:

151582

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74076

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000396

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

Alfa

AF:

0.0000434

Hom.:

ExAC

AF:

0.0000911

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

Jun 25, 2024

The c.5712C>G (p.C1904W) alteration is located in exon 32 (coding exon 32) of the ZFC3H1 gene. This alteration results from a C to G substitution at nucleotide position 5712, causing the cysteine (C) at amino acid position 1904 to be replaced by a tryptophan (W). 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

0.83

BayesDel_addAF

Benign

-0.0034

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.016

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.81

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.88

MVP

0.068

MPC

1.3

ClinPred

0.34

GERP RS

5.6

Varity_R

0.77

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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