rs370331986

Variant names:

• chr18-76379202-G-A
• rs370331986
• NM_014643.4:c.2912C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014643.4(ZNF516):​c.2912C>T​(p.Pro971Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000992 in 1,612,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P971P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000086 (0 hom.)
• Consequence: ZNF516 NM_014643.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.82
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023089588).

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.2912C>T	p.Pro971Leu	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.2912C>T	p.Pro971Leu	missense	Exon 4 of 7	ENSP00000394757.2	Q92618
	ZNF516	ENST00000617840.1	TSL:1	c.1082C>T	p.Pro361Leu	missense	Exon 1 of 3	ENSP00000478712.1	A0A087WUJ4
	ZNF516	ENST00000871208.1		c.2912C>T	p.Pro971Leu	missense	Exon 3 of 6	ENSP00000541267.1

Frequencies

GnomAD3 genomes AF: 0.000223 AC: 34 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000699

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000139 AC: 34 AN: 244928 AF XY: 0.000172

Gnomad AFR exome AF: 0.00110

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: 0.000109

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000863 AC: 126 AN: 1460568 Hom.: 0 Cov.: 32 AF XY: 0.0000908 AC XY: 66 AN XY: 726592

African (AFR) AF: 0.000866 AC: 29 AN: 33470

American (AMR) AF: 0.0000894 AC: 4 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000702 AC: 78 AN: 1111752

Other (OTH) AF: 0.0000994 AC: 6 AN: 60358

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152320 Hom.: 0 Cov.: 33 AF XY: 0.000269 AC XY: 20 AN XY: 74486

African (AFR) AF: 0.000697 AC: 29 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15314

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68004

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000175 Hom.: 0

Bravo AF: 0.000193

ESP6500AA AF: 0.000525 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000141 AC: 17

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

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	0.091
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T
Eigen	Benign	-0.00012
Eigen_PC	Benign	-0.024
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.98	T
PhyloP100		3.8
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.056
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.017	D
Polyphen		0.91	P
Vest4		0.14
MVP		0.12
MPC		0.074
ClinPred		0.084	T
GERP RS		2.9
PromoterAI		-0.00060	Neutral
Varity_R		0.081
gMVP		0.036
Mutation Taster		=91/9	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: rs370331986; hg19: chr18-74091158; COSMIC: COSV101487210; COSMIC: COSV101487210;