Variant 12-71619930-A-G 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_144982.5(ZFC3H1):c.5045T>C(p.Leu1682Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 32)

Consequence

ZFC3H1
NM_144982.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

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:

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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=0.03896287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFC3H1	NM_144982.5 linkuse as main transcript	c.5045T>C	p.Leu1682Ser	missense_variant	26/35	ENST00000378743.9
ZFC3H1	XM_047428485.1 linkuse as main transcript	c.3866T>C	p.Leu1289Ser	missense_variant	26/35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFC3H1	ENST00000378743.9 linkuse as main transcript	c.5045T>C	p.Leu1682Ser	missense_variant	26/35	1	NM_144982.5	P1	O60293-1
ZFC3H1	ENST00000552994.5 linkuse as main transcript	c.5045T>C	p.Leu1682Ser	missense_variant, NMD_transcript_variant	26/34	1			O60293-2
ZFC3H1	ENST00000546771.1 linkuse as main transcript	n.36T>C		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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

Apr 07, 2022

The c.5045T>C (p.L1682S) alteration is located in exon 26 (coding exon 26) of the ZFC3H1 gene. This alteration results from a T to C substitution at nucleotide position 5045, causing the leucine (L) at amino acid position 1682 to be replaced by a serine (S). 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

0.084

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.027

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.53

M_CAP

Benign

0.0017

MetaRNN

Benign

0.039

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.27

REVEL

Benign

0.013

Sift

Benign

0.50

Sift4G

Benign

0.58

Polyphen

0.0030

Vest4

0.10

MutPred

0.30

Gain of catalytic residue at R1685 (P = 0.0015);

MVP

0.043

MPC

0.48

ClinPred

0.032

GERP RS

0.043

Varity_R

0.021

gMVP

0.26

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