NM_001010851.3:c.10C>G

Variant names:

• chr19-52269623-C-G
• rs758862079
• NM_001010851.3:c.10C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001010851.3(ZNF766):​c.10C>G​(p.Leu4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF766 NM_001010851.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.296

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]

LOC124904763 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08248085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF766	NM_001010851.3	c.10C>G	p.Leu4Val	missense_variant	Exon 1 of 4	ENST00000439461.6	NP_001010851.1
LOC124904763	XR_007067331.1	n.990G>C		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF766	ENST00000439461.6	c.10C>G	p.Leu4Val	missense_variant	Exon 1 of 4	1	NM_001010851.3	ENSP00000409652.1
ZNF766	ENST00000599581.5	c.10C>G	p.Leu4Val	missense_variant	Exon 1 of 5	2		ENSP00000471965.1
ZNF766	ENST00000593703	c.-41C>G		5_prime_UTR_variant	Exon 1 of 3	4		ENSP00000469186.1
ZNF766	ENST00000601711	c.-334C>G		5_prime_UTR_variant	Exon 1 of 4	5		ENSP00000472743.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460658 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726702

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.10C>G (p.L4V) alteration is located in exon 1 (coding exon 1) of the ZNF766 gene. This alteration results from a C to G substitution at nucleotide position 10, causing the leucine (L) at amino acid position 4 to be replaced by a valine (V). 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	0.088
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.052	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.37	T;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.082	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.6	N;.
REVEL	Benign	0.018
Sift	Benign	0.052	T;.
Sift4G	Benign	0.11	T;T
Polyphen		0.019	B;.
Vest4		0.29
MutPred		0.34		Gain of MoRF binding (P = 0.0789);Gain of MoRF binding (P = 0.0789);
MVP		0.12
MPC		0.059
ClinPred		0.096	T
GERP RS		-0.67
Varity_R		0.093
gMVP		0.018

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs758862079; hg19: chr19-52772876;