rs778826784

Variant names:

• chr8-144807368-C-T
• rs778826784
• NM_213605.3:c.452C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-144807368-C-T
• chr8-144807368-C-A
• chr8-144807368-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_213605.3(ZNF517):​c.452C>T​(p.Pro151Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000579 in 1,555,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: ZNF517 NM_213605.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.42
• Publications: 0 publications found

Genes affected

ZNF517 (HGNC:27984): (zinc finger protein 517) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04367909).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213605.3. 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
	ZNF517	NM_213605.3	MANE Select	c.452C>T	p.Pro151Leu	missense	Exon 5 of 5	NP_998770.2	Q6ZMY9
	ZNF517	NM_001384904.1		c.452C>T	p.Pro151Leu	missense	Exon 5 of 5	NP_001371833.1	Q6ZMY9
	ZNF517	NM_001384905.1		c.452C>T	p.Pro151Leu	missense	Exon 6 of 6	NP_001371834.1	Q6ZMY9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF517	ENST00000359971.4	TSL:4 MANE Select	c.452C>T	p.Pro151Leu	missense	Exon 5 of 5	ENSP00000353058.3	Q6ZMY9
	ZNF517	ENST00000529429.5	TSL:1	c.350C>T	p.Pro117Leu	missense	Exon 3 of 3	ENSP00000432025.1	H0YCN3
	ZNF517	ENST00000525105.5	TSL:1	c.275-2738C>T		intron	N/A	ENSP00000433299.1	G3V191

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152200 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000313 AC: 5 AN: 159760 AF XY: 0.0000234

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000160

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000499 AC: 7 AN: 1403064 Hom.: 0 Cov.: 30 AF XY: 0.00000577 AC XY: 4 AN XY: 692878

African (AFR) AF: 0.00 AC: 0 AN: 31714

American (AMR) AF: 0.000111 AC: 4 AN: 36078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25018

East Asian (EAS) AF: 0.00 AC: 0 AN: 35934

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1081316

Other (OTH) AF: 0.00 AC: 0 AN: 58188

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152200 Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.000131 AC: 2 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.00000873 AC: 1

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	0.085
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.40
DANN	Benign	0.29
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.4
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.014
Sift	Benign	0.69	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.090
MutPred		0.22		Loss of glycosylation at P151 (P = 0.0522)
MVP		0.12
MPC		0.72
ClinPred		0.041	T
GERP RS		-1.8
Varity_R		0.032
gMVP		0.056
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: rs778826784; hg19: chr8-146032753;