rs1393669125

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080660.4(ZC3HAV1L):​c.336G>T​(p.Met112Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000302 in 1,324,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: 0.0000030 ( 0 hom. )

Consequence

ZC3HAV1L
NM_080660.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.217
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]

Genome browser will be placed here

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=0.060825795).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZC3HAV1LNM_080660.4 linkc.336G>T p.Met112Ile missense_variant Exon 1 of 5 ENST00000275766.2 NP_542391.2 Q96H79-1
ZC3HAV1LXM_011516688.4 linkc.336G>T p.Met112Ile missense_variant Exon 1 of 5 XP_011514990.1
ZC3HAV1LXM_006716176.4 linkc.336G>T p.Met112Ile missense_variant Exon 1 of 4 XP_006716239.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZC3HAV1LENST00000275766.2 linkc.336G>T p.Met112Ile missense_variant Exon 1 of 5 1 NM_080660.4 ENSP00000275766.1 Q96H79-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000400
AC:
3
AN:
75002
Hom.:
0
AF XY:
0.0000462
AC XY:
2
AN XY:
43250
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 SAS exome
AF:
0.000194
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000302
AC:
4
AN:
1324042
Hom.:
0
Cov.:
34
AF XY:
0.00000613
AC XY:
4
AN XY:
652484
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:
0.0000554
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.0040
T
Eigen
Benign
-0.50
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.43
T
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.061
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.50
N
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
0.21
N
REVEL
Benign
0.068
Sift
Benign
0.14
T
Sift4G
Benign
0.27
T
Polyphen
0.0
B
Vest4
0.17
MutPred
0.26
Gain of catalytic residue at M112 (P = 0.1922);
MVP
0.18
MPC
1.6
ClinPred
0.074
T
GERP RS
-0.036
Varity_R
0.16
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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.

Other links and lift over

dbSNP: rs1393669125; hg19: chr7-138720428; API