rs202041463

Variant names:

• chr16-3284188-G-A
• rs202041463
• NM_005741.5:c.370G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-3284188-G-A
• chr16-3284188-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005741.5(ZNF263):​c.370G>A​(p.Gly124Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,392,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G124W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: ZNF263 NM_005741.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73
• Publications: 0 publications found

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]

ACMG classification

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=0.17414883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF263	NM_005741.5	c.370G>A	p.Gly124Arg	missense_variant	Exon 1 of 6	ENST00000219069.6	NP_005732.2
ZNF263	NM_001411015.1	c.370G>A	p.Gly124Arg	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	c.370G>A	p.Gly124Arg	missense_variant	Exon 1 of 6	1	NM_005741.5	ENSP00000219069.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1392838 Hom.: 0 Cov.: 30 AF XY: 0.00000292 AC XY: 2 AN XY: 686026

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

African (AFR) AF: 0.0000635 AC: 2 AN: 31472

American (AMR) AF: 0.00 AC: 0 AN: 35302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21644

East Asian (EAS) AF: 0.00 AC: 0 AN: 38736

South Asian (SAS) AF: 0.00 AC: 0 AN: 76634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5460

European-Non Finnish (NFE) AF: 9.30e-7 AC: 1 AN: 1075624

Other (OTH) AF: 0.00 AC: 0 AN: 57256

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000042), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T;.;T;.
Eigen	Benign	-0.074
Eigen_PC	Benign	0.085
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.43	T;T;T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.28	N;.;.;.
PhyloP100		2.7
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.7	N;.;.;.
REVEL	Benign	0.078
Sift	Benign	0.060	T;.;.;.
Sift4G	Benign	0.33	T;T;T;T
Polyphen		0.29	B;.;.;.
Vest4		0.26
MutPred		0.51		Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);
MVP		0.18
MPC		0.50
ClinPred		0.81	D
GERP RS		4.9
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.5
Varity_R		0.30
gMVP		0.70
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs202041463; hg19: chr16-3334188;