Genetic Variant ZC3HAV1L:p.Ala92Ser (chr7-139035744-C-A) – 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.274G>T(p.Ala92Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000201 in 1,491,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

ZC3HAV1L
NM_080660.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.392

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:

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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=0.1708467).

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.274G>T	p.Ala92Ser	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.274G>T	p.Ala92Ser	missense	Exon 1 of 5	ENSP00000275766.1	Q96H79-1
ENSG00000304140	ENST00000799991.1		n.303+404C>A		intron	N/A
ENSG00000304140	ENST00000799992.1		n.-40C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152204

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000115

AC:

AN:

86898

AF XY:

0.0000203

show subpopulations

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:

0.000384

GnomAD4 exome

AF:

0.00000149

AC:

AN:

1338976

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

660072

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27038

American (AMR)

AF:

0.00

AC:

AN:

29392

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23678

East Asian (EAS)

AF:

0.00

AC:

AN:

29920

South Asian (SAS)

AF:

0.00

AC:

AN:

74522

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4208

European-Non Finnish (NFE)

AF:

0.00000188

AC:

AN:

1061302

Other (OTH)

AF:

0.00

AC:

AN:

55754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

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

Benign

0.11

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0040

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.51

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

-0.39

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.44

REVEL

Benign

0.032

Sift

Benign

0.19

Sift4G

Benign

0.30

Polyphen

0.87

Vest4

0.20

MutPred

0.32

Loss of methylation at R89 (P = 0.0717)

MVP

0.030

MPC

1.4

ClinPred

0.33

GERP RS

3.1

PromoterAI

0.0030

Neutral

(source)

Varity_R

0.12

gMVP

0.12

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over