7-139026552-C-T

Variant summary

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

The NM_080660.4(ZC3HAV1L):​c.895G>A​(p.Glu299Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,613,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

ZC3HAV1L
NM_080660.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0590
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=0.010496348).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZC3HAV1LNM_080660.4 linkc.895G>A p.Glu299Lys missense_variant Exon 5 of 5 ENST00000275766.2 NP_542391.2 Q96H79-1
ZC3HAV1LXM_011516688.4 linkc.886+156G>A intron_variant Intron 4 of 4 XP_011514990.1
ZC3HAV1LXM_006716176.4 linkc.*298G>A downstream_gene_variant XP_006716239.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZC3HAV1LENST00000275766.2 linkc.895G>A p.Glu299Lys missense_variant Exon 5 of 5 1 NM_080660.4 ENSP00000275766.1 Q96H79-1

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000851
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:
0.000955
GnomAD3 exomes
AF:
0.0000439
AC:
11
AN:
250362
Hom.:
0
AF XY:
0.0000369
AC XY:
5
AN XY:
135452
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000203
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000463
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000397
AC:
58
AN:
1461542
Hom.:
0
Cov.:
30
AF XY:
0.0000385
AC XY:
28
AN XY:
727116
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000335
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000369
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152316
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000850
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:
0.000945
Alfa
AF:
0.00000616
Hom.:
0
Bravo
AF:
0.000121
ExAC
AF:
0.0000741
AC:
9
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.895G>A (p.E299K) alteration is located in exon 5 (coding exon 5) of the ZC3HAV1L gene. This alteration results from a G to A substitution at nucleotide position 895, causing the glutamic acid (E) at amino acid position 299 to be replaced by a lysine (K). 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
0.075
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
19
DANN
Benign
0.96
DEOGEN2
Benign
0.0025
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.022
N
LIST_S2
Benign
0.30
T
M_CAP
Benign
0.0015
T
MetaRNN
Benign
0.010
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
0.17
N
REVEL
Benign
0.029
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.17
T
Polyphen
0.019
B
Vest4
0.18
MutPred
0.28
Gain of MoRF binding (P = 0);
MVP
0.014
MPC
0.26
ClinPred
0.12
T
GERP RS
-0.24
Varity_R
0.047
gMVP
0.31

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.

Other links and lift over

dbSNP: rs202173826; hg19: chr7-138711298; API