rs906653135

Variant names:

• chr16-89721732-G-A
• rs906653135
• NM_001113525.2:c.92G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-89721732-G-A
• chr16-89721732-G-C
• chr16-89721732-G-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.92G>A​(p.Arg31Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000167 in 1,194,990 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R31P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: ZNF276 NM_001113525.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• 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=0.20958179).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF276	NM_001113525.2	c.92G>A	p.Arg31Gln	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.92G>A	p.Arg31Gln	missense_variant	Exon 1 of 11	1	NM_001113525.2	ENSP00000415836.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000167 AC: 2 AN: 1194990 Hom.: 0 Cov.: 31 AF XY: 0.00000344 AC XY: 2 AN XY: 580598

⚠️ 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: 23946

American (AMR) AF: 0.00 AC: 0 AN: 11594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17132

East Asian (EAS) AF: 0.00 AC: 0 AN: 26904

South Asian (SAS) AF: 0.00 AC: 0 AN: 52286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27982

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3578

European-Non Finnish (NFE) AF: 0.00000203 AC: 2 AN: 983194

Other (OTH) AF: 0.00 AC: 0 AN: 48374

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.006664), 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	0.18
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.58	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.5
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.049
Sift	Uncertain	0.026	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.78	P
Vest4		0.17
MutPred		0.19		Loss of methylation at R31 (P = 0.0053);
MVP		0.040
MPC		0.13
ClinPred		0.17	T
GERP RS		3.5
PromoterAI		-0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.089
gMVP		0.12

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: rs906653135; hg19: chr16-89788140;