rs1208307719

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-89721684-C-G
• chr16-89721684-C-A
• chr16-89721684-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001113525.2(ZNF276):​c.44C>G​(p.Ser15Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000722 in 1,427,514 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: ZNF276 NM_001113525.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.012133211).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113525.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF276	NM_001113525.2	MANE Select	c.44C>G	p.Ser15Cys	missense	Exon 1 of 11	NP_001106997.1	Q8N554-1
	ZNF276	NM_152287.4		c.-21+408C>G		intron	N/A	NP_689500.2
	ZNF276	NR_110129.2		n.148C>G		non_coding_transcript_exon	Exon 1 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF276	ENST00000443381.7	TSL:1 MANE Select	c.44C>G	p.Ser15Cys	missense	Exon 1 of 11	ENSP00000415836.2	Q8N554-1
	ZNF276	ENST00000289816.9	TSL:1	c.-21+408C>G		intron	N/A	ENSP00000289816.5	Q8N554-2
	ZNF276	ENST00000950694.1		c.44C>G	p.Ser15Cys	missense	Exon 2 of 12	ENSP00000620753.1

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152124 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000206 AC: 10 AN: 48464 AF XY: 0.0000686

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00277

Gnomad NFE exome AF: 0.0000547

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000572 AC: 73 AN: 1275390 Hom.: 0 Cov.: 31 AF XY: 0.0000479 AC XY: 30 AN XY: 626812

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: 0.00209 AC: 66 AN: 31538

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

European-Non Finnish (NFE) AF: 0.00000487 AC: 5 AN: 1026318

Other (OTH) AF: 0.0000382 AC: 2 AN: 52306

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152124 Hom.: 0 Cov.: 34 AF XY: 0.000283 AC XY: 21 AN XY: 74318

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.0000655 AC: 1 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000106 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.87
DEOGEN2	Benign	0.047	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.15
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.086
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.068	T
Polyphen		0.21	B
Vest4		0.064
MutPred		0.11		Loss of phosphorylation at S15 (P = 0.0155)
MVP		0.11
MPC		0.075
ClinPred		0.032	T
GERP RS		0.58
PromoterAI		0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.066
gMVP		0.050
Mutation Taster		=95/5	polymorphism

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;