2-112236575-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_032494.3(ZC3H8):​c.491G>T​(p.Gly164Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000692 in 1,613,470 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G164D) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0038 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00037 ( 1 hom. )

Consequence

ZC3H8
NM_032494.3 missense

Scores

2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.389
Variant links:
Genes affected
ZC3H8 (HGNC:30941): (zinc finger CCCH-type containing 8) Enables RNA binding activity. Involved in several processes, including positive regulation of thymocyte apoptotic process; regulation of transcription, DNA-templated; and snRNA transcription. Located in Cajal body; histone locus body; and transcriptionally active chromatin. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]
FBLN7 (HGNC:26740): (fibulin 7) Predicted to enable calcium ion binding activity; heparan sulfate proteoglycan binding activity; and heparin binding activity. Predicted to be involved in cell adhesion. Predicted to act upstream of or within positive regulation of biomineralization. Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0052863955).
BS2
High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZC3H8NM_032494.3 linkc.491G>T p.Gly164Val missense_variant Exon 4 of 9 ENST00000409573.7 NP_115883.2 Q8N5P1
ZC3H8XR_001738994.2 linkn.552G>T non_coding_transcript_exon_variant Exon 4 of 9
FBLN7XR_007069507.1 linkn.10509-2546C>A intron_variant Intron 8 of 9
FBLN7XR_007069508.1 linkn.10508+5690C>A intron_variant Intron 8 of 8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZC3H8ENST00000409573.7 linkc.491G>T p.Gly164Val missense_variant Exon 4 of 9 5 NM_032494.3 ENSP00000386488.1 Q8N5P1
ZC3H8ENST00000466259.1 linkn.398G>T non_coding_transcript_exon_variant Exon 2 of 4 2
ZC3H8ENST00000474234.5 linkn.671G>T non_coding_transcript_exon_variant Exon 5 of 7 5
ZC3H8ENST00000464305.1 linkn.*11G>T downstream_gene_variant 5

Frequencies

GnomAD3 genomes
AF:
0.00381
AC:
580
AN:
152184
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0134
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00111
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.000845
AC:
210
AN:
248586
Hom.:
0
AF XY:
0.000556
AC XY:
75
AN XY:
134870
show subpopulations
Gnomad AFR exome
AF:
0.0125
Gnomad AMR exome
AF:
0.000408
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000329
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.000368
AC:
537
AN:
1461168
Hom.:
1
Cov.:
30
AF XY:
0.000297
AC XY:
216
AN XY:
726872
show subpopulations
Gnomad4 AFR exome
AF:
0.0135
Gnomad4 AMR exome
AF:
0.000606
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000895
GnomAD4 genome
AF:
0.00381
AC:
580
AN:
152302
Hom.:
3
Cov.:
32
AF XY:
0.00337
AC XY:
251
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0134
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000138
Hom.:
0
Bravo
AF:
0.00463
ExAC
AF:
0.00111
AC:
134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
17
DANN
Benign
0.81
DEOGEN2
Benign
0.075
T;T;T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.54
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.63
.;T;T
MetaRNN
Benign
0.0053
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.1
M;M;.
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-2.0
N;N;.
REVEL
Benign
0.069
Sift
Benign
0.083
T;T;.
Sift4G
Uncertain
0.0080
D;D;D
Polyphen
0.45
B;B;.
Vest4
0.13
MVP
0.13
MPC
0.20
ClinPred
0.013
T
GERP RS
3.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.15
gMVP
0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs76397380; hg19: chr2-112994152; API