NM_001113525.2:c.153G>T

Variant names:

• chr16-89721793-G-T
• rs1391462094
• NM_001113525.2:c.153G>T

Variant summary

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

The NM_001113525.2(ZNF276):​c.153G>T​(p.Trp51Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ZNF276 NM_001113525.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• 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: 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=0.12837958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF276	NM_001113525.2	c.153G>T	p.Trp51Cys	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.153G>T	p.Trp51Cys	missense_variant	Exon 1 of 11	1	NM_001113525.2	ENSP00000415836.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.43	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.12
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.065
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.023	D
Polyphen		0.0	B
Vest4		0.35
MutPred		0.35		Loss of MoRF binding (P = 0.0172);
MVP		0.014
MPC		0.20
ClinPred		0.12	T
GERP RS		0.024
PromoterAI		-0.056	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.5
Varity_R		0.096
gMVP		0.28

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: rs1391462094; hg19: chr16-89788201;