dbSNP rs1959250215: ZNF263:p.Thr91Ser (chr16-3284090-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005741.5(ZNF263):c.272C>G(p.Thr91Ser) 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 1,460,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. T91I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF263
NM_005741.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.917

Publications

0 publications found

Variant links:

Genes affected

ZNF263 (HGNC:13056): (zinc finger protein 263) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and transcription cis-regulatory region binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF263 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07027519).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF263	NM_005741.5 link	c.272C>G	p.Thr91Ser	missense_variant	Exon 1 of 6	ENST00000219069.6	NP_005732.2	O14978
ZNF263	NM_001411015.1 link	c.272C>G	p.Thr91Ser	missense_variant	Exon 1 of 8		NP_001397944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF263	ENST00000219069.6 link	c.272C>G	p.Thr91Ser	missense_variant	Exon 1 of 6	1	NM_005741.5	ENSP00000219069.5		O14978

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1460974

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726842

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.00

AC:

AN:

86196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111510

Other (OTH)

AF:

0.00

AC:

AN:

60342

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.8

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.048

T;.;T;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.24

T;T;T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.070

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.7

L;.;.;.

PhyloP100

-0.92

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.88

N;.;.;.

REVEL

Benign

0.053

Sift

Benign

1.0

T;.;.;.

Sift4G

Benign

0.57

T;T;T;T

Polyphen

0.052

B;.;.;.

Vest4

0.056

MutPred

0.55

Gain of disorder (P = 0.0542);Gain of disorder (P = 0.0542);Gain of disorder (P = 0.0542);Gain of disorder (P = 0.0542);

MVP

0.040

MPC

0.45

ClinPred

0.32

GERP RS

3.0

PromoterAI

-0.093

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.051

gMVP

0.37

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over