chr8-144807424-C-T

Variant names:

• chr8-144807424-C-T
• rs1261567685
• NM_213605.3:c.508C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_213605.3(ZNF517):​c.508C>T​(p.Pro170Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,416,326 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF517 NM_213605.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.272

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07417771).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF517	NM_213605.3	c.508C>T	p.Pro170Ser	missense_variant	Exon 5 of 5	ENST00000359971.4	NP_998770.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF517	ENST00000359971.4	c.508C>T	p.Pro170Ser	missense_variant	Exon 5 of 5	4	NM_213605.3	ENSP00000353058.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1416326 Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1 AN XY: 700808

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000184

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.508C>T (p.P170S) alteration is located in exon 5 (coding exon 4) of the ZNF517 gene. This alteration results from a C to T substitution at nucleotide position 508, causing the proline (P) at amino acid position 170 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.0
DANN	Benign	0.23
DEOGEN2	Benign	0.0032	T;T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.27	T;.
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.17	N;N
REVEL	Benign	0.023
Sift	Benign	0.70	T;T
Sift4G	Benign	0.70	T;T
Polyphen		0.33	B;B
Vest4		0.065
MutPred		0.23		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.12
MPC		0.66
ClinPred		0.14	T
GERP RS		2.4
Varity_R		0.021
gMVP		0.070

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

Publications

LitVar

Other links and lift over

dbSNP: rs1261567685; hg19: chr8-146032809;