Genetic Variant ZC3HAV1L:p.Met112Ile (chr7-139035682-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080660.4(ZC3HAV1L):c.336G>A(p.Met112Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000982 in 1,324,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000098 ( 0 hom. )

Consequence

ZC3HAV1L
NM_080660.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.217

Publications

0 publications found

Variant links:

Genes affected

ZC3HAV1L (HGNC:22423): (zinc finger CCCH-type containing, antiviral 1 like) Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ZC3HAV1L links:

ENSG00000304140 (HGNC:):

ENSG00000304140 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.068581104).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080660.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3HAV1L	NM_080660.4	MANE Select	c.336G>A	p.Met112Ile	missense	Exon 1 of 5	NP_542391.2	Q96H79-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZC3HAV1L	ENST00000275766.2	TSL:1 MANE Select	c.336G>A	p.Met112Ile	missense	Exon 1 of 5	ENSP00000275766.1	Q96H79-1
ENSG00000304140	ENST00000799991.1		n.303+342C>T		intron	N/A
ENSG00000304140	ENST00000799992.1		n.-102C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

75002

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000982

AC:

AN:

1324042

Hom.:

Cov.:

AF XY:

0.0000107

AC XY:

AN XY:

652484

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26654

American (AMR)

AF:

0.00

AC:

AN:

26058

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22876

East Asian (EAS)

AF:

0.00

AC:

AN:

29282

South Asian (SAS)

AF:

0.00

AC:

AN:

72148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32840

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4106

European-Non Finnish (NFE)

AF:

0.0000114

AC:

AN:

1055034

Other (OTH)

AF:

0.0000182

AC:

AN:

55044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0040

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.43

M_CAP

Benign

0.026

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.50

PhyloP100

0.22

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.21

REVEL

Benign

0.068

Sift

Benign

0.14

Sift4G

Benign

0.27

Polyphen

0.0

Vest4

0.17

MutPred

0.26

Gain of catalytic residue at M112 (P = 0.1922)

MVP

0.18

MPC

1.6

ClinPred

0.096

GERP RS

-0.036

PromoterAI

0.29

Neutral

(source)

Varity_R

0.16

gMVP

0.26

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over