chr16-89721645-A-C

Variant names:

• chr16-89721645-A-C
• rs984956130
• NM_001113525.2:c.5A>C

Variant summary

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

The NM_001113525.2(ZNF276):​c.5A>C​(p.Lys2Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000759 in 1,318,234 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K2R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: ZNF276 NM_001113525.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• 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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF276	NM_001113525.2	c.5A>C	p.Lys2Thr	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.5A>C	p.Lys2Thr	missense_variant	Exon 1 of 11	1	NM_001113525.2	ENSP00000415836.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.59e-7 AC: 1 AN: 1318234 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 650158

African (AFR) AF: 0.00 AC: 0 AN: 26790

American (AMR) AF: 0.00 AC: 0 AN: 26582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23270

East Asian (EAS) AF: 0.00 AC: 0 AN: 27912

South Asian (SAS) AF: 0.00 AC: 0 AN: 73198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4836

European-Non Finnish (NFE) AF: 9.54e-7 AC: 1 AN: 1048422

Other (OTH) AF: 0.00 AC: 0 AN: 54534

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.066
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.43	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.2
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.073
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.20
MutPred		0.19		Gain of phosphorylation at K2 (P = 0.0056);
MVP		0.45
MPC		0.44
ClinPred		0.76	D
GERP RS		2.8
PromoterAI		0.32	Neutral
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.3
Varity_R		0.17
gMVP		0.085

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: rs984956130; hg19: chr16-89788053;