dbSNP rs201232871: ZNF326:p.Asp6Gly (chr1-89998110-A-G) – ACMG Classification: Uncertain_significance (1 pts)

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 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF326
NM_182976.4 missense, splice_region

Scores

Splicing: ADA: 0.5809

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]

ZNF326 links:

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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
ZNF326	NM_182976.4 link	c.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	UniProt
ZNF326	ENST00000340281.9 link	c.17A>G	p.Asp6Gly	missense_variant, splice_region_variant	Exon 2 of 12	1	NM_182976.4	ENSP00000340796.4	Q5BKZ1-1
ZNF326	ENST00000370447.3 link	c.17A>G	p.Asp6Gly	missense_variant, splice_region_variant	Exon 2 of 12	1		ENSP00000359476.2	A0A0A0MRN4
ZNF326	ENST00000361911.9 link	c.17A>G	p.Asp6Gly	missense_variant, splice_region_variant	Exon 2 of 4	1		ENSP00000355318.5	Q5BKZ1-2
ZNF326	ENST00000394583.7 link	n.17A>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 10	1		ENSP00000378084.3	E2QRN4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460514

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

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.:

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

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

T;.;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.0054

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.79

T;T;T

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.40

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N;.

PrimateAI

Uncertain

0.72

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over