8-144807301-G-A

Variant names:

• chr8-144807301-G-A
• rs779249597
• NM_213605.3:c.385G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_213605.3(ZNF517):​c.385G>A​(p.Gly129Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ZNF517 NM_213605.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.33
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089696884).

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.385G>A	p.Gly129Arg	missense	Exon 5 of 5	NP_998770.2	Q6ZMY9
	ZNF517	NM_001384904.1		c.385G>A	p.Gly129Arg	missense	Exon 5 of 5	NP_001371833.1	Q6ZMY9
	ZNF517	NM_001384905.1		c.385G>A	p.Gly129Arg	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.385G>A	p.Gly129Arg	missense	Exon 5 of 5	ENSP00000353058.3	Q6ZMY9
	ZNF517	ENST00000529429.5	TSL:1	c.283G>A	p.Gly95Arg	missense	Exon 3 of 3	ENSP00000432025.1	H0YCN3
	ZNF517	ENST00000525105.5	TSL:1	c.275-2805G>A		intron	N/A	ENSP00000433299.1	G3V191

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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	0.17
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.90
DANN	Benign	0.43
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.021
Sift	Benign	0.60	T
Sift4G	Benign	0.58	T
Polyphen		0.11	B
Vest4		0.12
MutPred		0.19		Gain of catalytic residue at G129 (P = 0.069)
MVP		0.15
MPC		0.33
ClinPred		0.054	T
Varity_R		0.058
gMVP		0.087
Mutation Taster		=100/0	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: rs779249597; hg19: chr8-146032686;