dbSNP rs556332273: ZNF496:p.Gln287Arg (chr1-247309731-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032752.3(ZNF496):c.860A>G(p.Gln287Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. Q287P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF496
NM_032752.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.04

Variant links:

Genes affected

ZNF496 (HGNC:23713): (zinc finger protein 496) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and protein self-association. Predicted to be involved in positive regulation of transcription, DNA-templated and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Predicted to be located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ZNF496 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15961865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF496	NM_032752.3 link	c.860A>G	p.Gln287Arg	missense_variant	Exon 8 of 10	ENST00000682384.1	NP_116141.1	Q96IT1-1
ZNF496	NM_001329733.2 link	c.860A>G	p.Gln287Arg	missense_variant	Exon 8 of 10		NP_001316662.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF496	ENST00000682384.1 link	c.860A>G	p.Gln287Arg	missense_variant	Exon 8 of 10		NM_032752.3	ENSP00000507236.1	Q96IT1-1
ZNF496	ENST00000294753.8 link	c.860A>G	p.Gln287Arg	missense_variant	Exon 7 of 9	1		ENSP00000294753.4	Q96IT1-1
ZNF496	ENST00000461277.2 link	c.635A>G	p.Gln212Arg	missense_variant	Exon 6 of 8	1		ENSP00000473324.1	A0A0C4DGR5
ZNF496	ENST00000462139.1 link	n.4122A>G		non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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

Benign

0.13

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.038

T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.4

N;.

REVEL

Benign

0.063

Sift

Benign

0.077

T;.

Sift4G

Uncertain

0.057

T;T

Polyphen

0.98

D;.

Vest4

0.35

MutPred

0.29

Loss of glycosylation at K289 (P = 0.2135);.;

MVP

0.23

MPC

1.2

ClinPred

0.51

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.042

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

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