16-3286051-T-C

Position:

• chr16-3286051-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005741.5(ZNF263):​c.671T>C​(p.Met224Thr) 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 1,461,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF263 NM_005741.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93

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]

ENSG00000290183 (HGNC:):

ACMG classification

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=0.14140454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF263	NM_005741.5	c.671T>C	p.Met224Thr	missense_variant	4/6	ENST00000219069.6	NP_005732.2
ZNF263	NM_001411015.1	c.671T>C	p.Met224Thr	missense_variant	4/8		NP_001397944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF263	ENST00000219069.6	c.671T>C	p.Met224Thr	missense_variant	4/6	1	NM_005741.5	ENSP00000219069.5
ENSG00000290183	ENST00000703449.1	c.-170-3342T>C		intron_variant				ENSP00000515300.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461396 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727022

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 24, 2024

The c.671T>C (p.M224T) alteration is located in exon 4 (coding exon 4) of the ZNF263 gene. This alteration results from a T to C substitution at nucleotide position 671, causing the methionine (M) at amino acid position 224 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	22
DANN	Benign	0.68
DEOGEN2	Benign	0.035	T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.0016
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.9	N;.
REVEL	Benign	0.096
Sift	Uncertain	0.011	D;.
Sift4G	Uncertain	0.016	D;D
Polyphen		0.0	B;.
Vest4		0.58
MutPred		0.45		Loss of stability (P = 0.0248);.;
MVP		0.45
MPC		0.24
ClinPred		0.15	T
GERP RS		4.9
Varity_R		0.23
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs912811087; hg19: chr16-3336051;