NM_001113525.2:c.106C>T

Variant names:

• chr16-89721746-C-T
• rs867357431
• NM_001113525.2:c.106C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001113525.2(ZNF276):​c.106C>T​(p.Leu36Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,322,602 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00016 (1 hom., cov: 34)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: ZNF276 NM_001113525.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.362
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00927794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF276	NM_001113525.2	c.106C>T	p.Leu36Phe	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.106C>T	p.Leu36Phe	missense_variant	Exon 1 of 11	1	NM_001113525.2	ENSP00000415836.2

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152032 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000468 AC: 2 AN: 4278 AF XY: 0.000355

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00360

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000105 AC: 123 AN: 1170462 Hom.: 0 Cov.: 31 AF XY: 0.0000936 AC XY: 53 AN XY: 566202

African (AFR) AF: 0.000171 AC: 4 AN: 23440

American (AMR) AF: 0.000934 AC: 9 AN: 9636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16052

East Asian (EAS) AF: 0.00 AC: 0 AN: 26732

South Asian (SAS) AF: 0.0000430 AC: 2 AN: 46516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26830

Middle Eastern (MID) AF: 0.00267 AC: 9 AN: 3368

European-Non Finnish (NFE) AF: 0.0000886 AC: 86 AN: 970694

Other (OTH) AF: 0.000275 AC: 13 AN: 47194

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152140 Hom.: 1 Cov.: 34 AF XY: 0.000188 AC XY: 14 AN XY: 74398

African (AFR) AF: 0.0000722 AC: 3 AN: 41538

American (AMR) AF: 0.000654 AC: 10 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67958

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000162

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.106C>T (p.L36F) alteration is located in exon 1 (coding exon 1) of the ZNF276 gene. This alteration results from a C to T substitution at nucleotide position 106, causing the leucine (L) at amino acid position 36 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.053	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.0093	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.36
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.041
Sift	Benign	0.064	T
Sift4G	Benign	0.068	T
Polyphen		0.072	B
Vest4		0.039
MutPred		0.14		Loss of glycosylation at S35 (P = 0.1152);
MVP		0.076
MPC		0.074
ClinPred		0.023	T
GERP RS		0.53
PromoterAI		0.028	Neutral
Varity_R		0.041
gMVP		0.032
Mutation Taster		=98/2	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: rs867357431; hg19: chr16-89788154;