rs372078590

Variant names:

• chr18-76379115-C-T
• rs372078590
• NM_014643.4:c.2999G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014643.4(ZNF516):​c.2999G>A​(p.Arg1000His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000067 in 1,611,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1000C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: ZNF516 NM_014643.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.271
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10762489).

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.2999G>A	p.Arg1000His	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.2999G>A	p.Arg1000His	missense	Exon 4 of 7	ENSP00000394757.2	Q92618
	ZNF516	ENST00000617840.1	TSL:1	c.1169G>A	p.Arg390His	missense	Exon 1 of 3	ENSP00000478712.1	A0A087WUJ4
	ZNF516	ENST00000871208.1		c.2999G>A	p.Arg1000His	missense	Exon 3 of 6	ENSP00000541267.1

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152100 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000620 AC: 15 AN: 241872 AF XY: 0.0000679

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000170

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000462

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000658 AC: 96 AN: 1459836 Hom.: 0 Cov.: 32 AF XY: 0.0000509 AC XY: 37 AN XY: 726296

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.0000224 AC: 1 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39694

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000585 AC: 65 AN: 1111680

Other (OTH) AF: 0.0000994 AC: 6 AN: 60334

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152100 Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7 AN XY: 74296

African (AFR) AF: 0.00 AC: 0 AN: 41414

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000124 AC: 1

ExAC AF: 0.0000666 AC: 8

Asia WGS AF: 0.000866 AC: 3 AN: 3478

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	0.14
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.27
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.043
Sift	Benign	0.032	D
Sift4G	Benign	0.32	T
Polyphen		1.0	D
Vest4		0.23
MVP		0.13
MPC		0.084
ClinPred		0.18	T
GERP RS		2.9
PromoterAI		0.0064	Neutral
Varity_R		0.057
gMVP		0.12
Mutation Taster		=99/1	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: rs372078590; hg19: chr18-74091071;