chr16-89721684-C-A

Variant names:

• chr16-89721684-C-A
• rs1208307719
• NM_001113525.2:c.44C>A

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.44C>A​(p.Ser15Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000784 in 1,275,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S15C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: ZNF276 NM_001113525.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152
• 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=0.09327641).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF276	NM_001113525.2	c.44C>A	p.Ser15Tyr	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.44C>A	p.Ser15Tyr	missense_variant	Exon 1 of 11	1	NM_001113525.2	ENSP00000415836.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.84e-7 AC: 1 AN: 1275390 Hom.: 0 Cov.: 31 AF XY: 0.00000160 AC XY: 1 AN XY: 626812

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25544

American (AMR) AF: 0.00 AC: 0 AN: 18756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21346

East Asian (EAS) AF: 0.00 AC: 0 AN: 27460

South Asian (SAS) AF: 0.00 AC: 0 AN: 67594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4528

European-Non Finnish (NFE) AF: 9.74e-7 AC: 1 AN: 1026318

Other (OTH) AF: 0.00 AC: 0 AN: 52306

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.85
DEOGEN2	Benign	0.047	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.15
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.038
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.046	D
Polyphen		0.45	P
Vest4		0.090
MutPred		0.21		Gain of catalytic residue at S15 (P = 0.0347);
MVP		0.14
MPC		0.093
ClinPred		0.073	T
GERP RS		0.58
PromoterAI		0.089	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.047
gMVP		0.057

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: rs1208307719; hg19: chr16-89788092;