18-76378900-G-T

Variant names:

• chr18-76378900-G-T
• rs762133977
• NM_014643.4:c.3214C>A

Variant summary

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

The NM_014643.4(ZNF516):​c.3214C>A​(p.Leu1072Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF516 NM_014643.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64
• Publications: 0 publications found

Genes affected

ZNF516 (HGNC:28990): (zinc finger protein 516) Zinc-finger proteins bind nucleic acids and play important roles in various cellular functions, including cell proliferation, differentiation, and apoptosis. This gene encodes a zinc-finger protein, and belongs to the krueppel C2H2-type zinc-finger protein family. It may be involved in transcriptional regulation. [provided by RefSeq, Sep 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014643.4. 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
	ZNF516	NM_014643.4	MANE Select	c.3214C>A	p.Leu1072Ile	missense	Exon 4 of 7	NP_055458.1	Q92618

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF516	ENST00000443185.7	TSL:1 MANE Select	c.3214C>A	p.Leu1072Ile	missense	Exon 4 of 7	ENSP00000394757.2	Q92618
	ZNF516	ENST00000617840.1	TSL:1	c.1384C>A	p.Leu462Ile	missense	Exon 1 of 3	ENSP00000478712.1	A0A087WUJ4
	ZNF516	ENST00000871208.1		c.3214C>A	p.Leu1072Ile	missense	Exon 3 of 6	ENSP00000541267.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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	0.19
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.098	T
Eigen	Benign	0.045
Eigen_PC	Benign	-0.017
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.6
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.029	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.36		Loss of helix (P = 0.0138)
MVP		0.10
MPC		0.42
ClinPred		0.88	D
GERP RS		4.0
PromoterAI		0.068	Neutral
Varity_R		0.41
gMVP		0.22

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: rs762133977; hg19: chr18-74090855;