rs201232871

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_182976.4(ZNF326):​c.17A>G​(p.Asp6Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. D6V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

ZNF326
NM_182976.4 missense, splice_region

Scores

2
5
12
Splicing: ADA: 0.5809
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.29
Variant links:
Genes affected
ZNF326 (HGNC:14104): (zinc finger protein 326) Enables RNA polymerase II complex binding activity. Involved in regulation of DNA-templated transcription, elongation and regulation of RNA splicing. Located in nucleoplasm. Part of DBIRD complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.4033016).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF326NM_182976.4 linkc.17A>G p.Asp6Gly missense_variant, splice_region_variant Exon 2 of 12 ENST00000340281.9 NP_892021.1 Q5BKZ1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF326ENST00000340281.9 linkc.17A>G p.Asp6Gly missense_variant, splice_region_variant Exon 2 of 12 1 NM_182976.4 ENSP00000340796.4 Q5BKZ1-1
ZNF326ENST00000370447.3 linkc.17A>G p.Asp6Gly missense_variant, splice_region_variant Exon 2 of 12 1 ENSP00000359476.2 A0A0A0MRN4
ZNF326ENST00000361911.9 linkc.17A>G p.Asp6Gly missense_variant, splice_region_variant Exon 2 of 4 1 ENSP00000355318.5 Q5BKZ1-2
ZNF326ENST00000394583.7 linkn.17A>G splice_region_variant, non_coding_transcript_exon_variant Exon 2 of 10 1 ENSP00000378084.3 E2QRN4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460514
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726544
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.44
BayesDel_addAF
Benign
-0.057
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.019
T;.;.
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.0054
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.79
T;T;T
M_CAP
Pathogenic
0.48
D
MetaRNN
Benign
0.40
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N;N;.
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
0.19
N;D;N
REVEL
Benign
0.16
Sift
Uncertain
0.014
D;D;T
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.49
P;.;.
Vest4
0.67
MutPred
0.13
Loss of stability (P = 0.0983);Loss of stability (P = 0.0983);Loss of stability (P = 0.0983);
MVP
0.23
MPC
0.40
ClinPred
0.72
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.13
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.58
dbscSNV1_RF
Benign
0.52
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-90463669; API