NM_001010851.3:c.380A>C

Variant names:

• chr19-52290171-A-C
• NM_001010851.3:c.380A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001010851.3(ZNF766):​c.380A>C​(p.Glu127Ala) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF766 NM_001010851.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.193
• 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]

ENSG00000269102 (HGNC:):

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=0.12662542).

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.380A>C	p.Glu127Ala	missense	Exon 4 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.380A>C	p.Glu127Ala	missense	Exon 4 of 4	ENSP00000409652.1	Q5HY98
	ZNF766	ENST00000950441.1		c.410A>C	p.Glu137Ala	missense	Exon 5 of 5	ENSP00000620500.1
	ZNF766	ENST00000593612.1	TSL:2	c.425A>C	p.Glu142Ala	missense	Exon 5 of 6	ENSP00000468950.1	G3XAE0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.6
DANN	Benign	0.90
DEOGEN2	Benign	0.21	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.19
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.019
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.055	T
Polyphen		0.19	B
Vest4		0.083
MutPred		0.39		Gain of catalytic residue at E142 (P = 0.0527)
MVP		0.14
MPC		0.050
ClinPred		0.11	T
GERP RS		1.4
Varity_R		0.10
gMVP		0.037
Mutation Taster		=100/0	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

hg19: chr19-52793424;