16-89722784-C-A

Variant summary

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

The NM_001113525.2(ZNF276):c.459C>A(p.Phe153Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ZNF276 NM_001113525.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.407

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF276	NM_001113525.2	c.459C>A	p.Phe153Leu	missense_variant	2/11	ENST00000443381.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF276	ENST00000443381.7	c.459C>A	p.Phe153Leu	missense_variant	2/11	1	NM_001113525.2	P2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

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

Aug 04, 2023

The c.459C>A (p.F153L) alteration is located in exon 2 (coding exon 2) of the ZNF276 gene. This alteration results from a C to A substitution at nucleotide position 459, causing the phenylalanine (F) at amino acid position 153 to be replaced by a leucine (L). 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Benign	0.071
Eigen_PC	Benign	0.030
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.42	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.86
MutPred		0.50		.;.;Gain of loop (P = 0.0166);
MVP		0.19
MPC		0.44
ClinPred		0.98	D
GERP RS		2.6
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.7
Varity_R		0.47
gMVP		0.47

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-89789192;