NM_001113525.2:c.104C>G

Variant names:

• chr16-89721744-C-G
• rs1333948565
• NM_001113525.2:c.104C>G

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.104C>G​(p.Ser35Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000171 in 1,171,152 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. S35F) 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: -0.0470
• 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=0.086925596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF276	NM_001113525.2	c.104C>G	p.Ser35Cys	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.104C>G	p.Ser35Cys	missense_variant	Exon 1 of 11	1	NM_001113525.2	ENSP00000415836.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000171 AC: 2 AN: 1171152 Hom.: 0 Cov.: 31 AF XY: 0.00000176 AC XY: 1 AN XY: 566646

African (AFR) AF: 0.00 AC: 0 AN: 23444

American (AMR) AF: 0.00 AC: 0 AN: 9646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16090

East Asian (EAS) AF: 0.00 AC: 0 AN: 26742

South Asian (SAS) AF: 0.00 AC: 0 AN: 46682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26860

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3378

European-Non Finnish (NFE) AF: 0.00000206 AC: 2 AN: 971066

Other (OTH) AF: 0.00 AC: 0 AN: 47244

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	17
DANN	Benign	0.86
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.047
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.058
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.016	D
Polyphen		0.21	B
Vest4		0.096
MutPred		0.19		Loss of phosphorylation at S35 (P = 0.0057);
MVP		0.014
MPC		0.10
ClinPred		0.15	T
GERP RS		2.9
PromoterAI		0.0057	Neutral
Varity_R		0.11
gMVP		0.069
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1333948565; hg19: chr16-89788152;