8-144807206-C-T

Variant names:

• chr8-144807206-C-T
• NM_213605.3:c.290C>T

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.290C>T​(p.Ala97Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,376,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: ZNF517 NM_213605.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.233
• 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=0.06321475).

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.290C>T	p.Ala97Val	missense	Exon 5 of 5	NP_998770.2	Q6ZMY9
	ZNF517	NM_001384904.1		c.290C>T	p.Ala97Val	missense	Exon 5 of 5	NP_001371833.1	Q6ZMY9
	ZNF517	NM_001384905.1		c.290C>T	p.Ala97Val	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.290C>T	p.Ala97Val	missense	Exon 5 of 5	ENSP00000353058.3	Q6ZMY9
	ZNF517	ENST00000529429.5	TSL:1	c.188C>T	p.Ala63Val	missense	Exon 3 of 3	ENSP00000432025.1	H0YCN3
	ZNF517	ENST00000525105.5	TSL:1	c.275-2900C>T		intron	N/A	ENSP00000433299.1	G3V191

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000218 AC: 3 AN: 1376328 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 676214

African (AFR) AF: 0.00 AC: 0 AN: 30426

American (AMR) AF: 0.00 AC: 0 AN: 29974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20698

East Asian (EAS) AF: 0.00 AC: 0 AN: 38918

South Asian (SAS) AF: 0.00 AC: 0 AN: 72660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5378

European-Non Finnish (NFE) AF: 0.00000280 AC: 3 AN: 1072228

Other (OTH) AF: 0.00 AC: 0 AN: 56592

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	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.23
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.0080
Sift	Benign	0.23	T
Sift4G	Benign	0.30	T
Polyphen		0.12	B
Vest4		0.077
MutPred		0.26		Gain of catalytic residue at D92 (P = 0.0608)
MVP		0.099
MPC		0.27
ClinPred		0.075	T
GERP RS		1.6
Varity_R		0.026
gMVP		0.13
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

hg19: chr8-146032591;