chr16-89721794-G-T

Variant names:

• chr16-89721794-G-T
• rs533389782
• NM_001113525.2:c.154G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001113525.2(ZNF276):​c.154G>T​(p.Gly52Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,256,198 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 34)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: ZNF276 NM_001113525.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.153
• Publications: 0 publications found

Genes affected

ZNF276 (HGNC:23330): (zinc finger protein 276) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in kinetochore. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011316508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF276	NM_001113525.2	c.154G>T	p.Gly52Cys	missense_variant	Exon 1 of 11	ENST00000443381.7	NP_001106997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF276	ENST00000443381.7	c.154G>T	p.Gly52Cys	missense_variant	Exon 1 of 11	1	NM_001113525.2	ENSP00000415836.2

Frequencies

GnomAD3 genomes AF: 0.00107 AC: 162 AN: 151916 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.00355

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.00 AC: 0 AN: 290 AF XY: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000123 AC: 136 AN: 1104176 Hom.: 0 Cov.: 31 AF XY: 0.000101 AC XY: 53 AN XY: 526312

African (AFR) AF: 0.00526 AC: 119 AN: 22626

American (AMR) AF: 0.000492 AC: 4 AN: 8128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14388

East Asian (EAS) AF: 0.00 AC: 0 AN: 25878

South Asian (SAS) AF: 0.00 AC: 0 AN: 29660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22992

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2944

European-Non Finnish (NFE) AF: 0.00000321 AC: 3 AN: 933344

Other (OTH) AF: 0.000226 AC: 10 AN: 44216

GnomAD4 genome AF: 0.00106 AC: 161 AN: 152022 Hom.: 1 Cov.: 34 AF XY: 0.000995 AC XY: 74 AN XY: 74346

African (AFR) AF: 0.00352 AC: 146 AN: 41526

American (AMR) AF: 0.000655 AC: 10 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67946

Other (OTH) AF: 0.00237 AC: 5 AN: 2106

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00134

ExAC AF: 0.000421 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.154G>T (p.G52C) alteration is located in exon 1 (coding exon 1) of the ZNF276 gene. This alteration results from a G to T substitution at nucleotide position 154, causing the glycine (G) at amino acid position 52 to be replaced by a cysteine (C). 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	0.26
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.31	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.15
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.069
Sift	Benign	0.073	T
Sift4G	Uncertain	0.028	D
Polyphen		0.76	P
Vest4		0.13
MutPred		0.29		Gain of helix (P = 0.0022);
MVP		0.085
MPC		0.18
ClinPred		0.26	T
GERP RS		1.9
PromoterAI		-0.078	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.5
Varity_R		0.088
gMVP		0.21
Mutation Taster		=88/12	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: rs533389782; hg19: chr16-89788202;