rs220379

Variant names:

• chr16-3289435-G-A
• rs220379
• NM_005741.5:c.929G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-3289435-G-A
• chr16-3289435-G-C
• chr16-3289435-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005741.5(ZNF263):​c.929G>A​(p.Cys310Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 1,371,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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: -1.24
• Publications: 41 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053321242).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005741.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF263	NM_005741.5	MANE Select	c.929G>A	p.Cys310Tyr	missense	Exon 6 of 6	NP_005732.2
	ZNF263	NM_001411015.1		c.929G>A	p.Cys310Tyr	missense	Exon 6 of 8	NP_001397944.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF263	ENST00000219069.6	TSL:1 MANE Select	c.929G>A	p.Cys310Tyr	missense	Exon 6 of 6	ENSP00000219069.5
	ZNF263	ENST00000574674.2	TSL:2	c.929G>A	p.Cys310Tyr	missense	Exon 6 of 8	ENSP00000461755.2
	ZNF263	ENST00000575332.2	TSL:3	c.929G>A	p.Cys310Tyr	missense	Exon 6 of 7	ENSP00000461146.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000559 AC: 1 AN: 178864 AF XY: 0.0000106

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000219 AC: 3 AN: 1371912 Hom.: 0 Cov.: 33 AF XY: 0.00000297 AC XY: 2 AN XY: 673366

African (AFR) AF: 0.00 AC: 0 AN: 30316

American (AMR) AF: 0.00 AC: 0 AN: 29252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19992

East Asian (EAS) AF: 0.00 AC: 0 AN: 39048

South Asian (SAS) AF: 0.0000142 AC: 1 AN: 70590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5322

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1071002

Other (OTH) AF: 0.00 AC: 0 AN: 56450

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000848 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.95
DANN	Benign	0.95
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.053	T
PhyloP100		-1.2
Sift4G	Benign	0.38	T
Vest4		0.13
MVP		0.014
ClinPred		0.056	T
GERP RS		-0.92
Varity_R		0.043
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs220379; hg19: chr16-3339435;