19-52283338-C-T

Variant names:

• chr19-52283338-C-T
• rs1333929287
• NM_001010851.3:c.199C>T

Variant summary

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

The NM_001010851.3(ZNF766):​c.199C>T​(p.Pro67Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF766 NM_001010851.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.301
• Publications: 0 publications found

Genes affected

ZNF766 (HGNC:28063): (zinc finger protein 766) Predicted to enable DNA binding activity and metal ion binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Located in nucleus. [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=0.063682795).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010851.3. 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
	ZNF766	NM_001010851.3	MANE Select	c.199C>T	p.Pro67Ser	missense	Exon 3 of 4	NP_001010851.1	Q5HY98

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF766	ENST00000439461.6	TSL:1 MANE Select	c.199C>T	p.Pro67Ser	missense	Exon 3 of 4	ENSP00000409652.1	Q5HY98
	ZNF766	ENST00000950441.1		c.229C>T	p.Pro77Ser	missense	Exon 4 of 5	ENSP00000620500.1
	ZNF766	ENST00000593612.1	TSL:2	c.244C>T	p.Pro82Ser	missense	Exon 4 of 6	ENSP00000468950.1	G3XAE0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249414 AF XY: 0.00000739

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: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Uncertain	0.42
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.1
DANN	Benign	0.72
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.049	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.30
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.037
Sift	Benign	0.42	T
Sift4G	Benign	0.14	T
Polyphen		0.055	B
Vest4		0.19
MutPred		0.29		Gain of phosphorylation at P82 (P = 0.0699)
MVP		0.30
MPC		0.17
ClinPred		0.065	T
GERP RS		-4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.036
gMVP		0.056
Mutation Taster		=90/10	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: rs1333929287; hg19: chr19-52786591;