chr8-144807424-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.272
Variant links:
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]

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ACMG classification

Classification made for transcript

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
ZNF517NM_213605.3 linkc.508C>T p.Pro170Ser missense_variant Exon 5 of 5 ENST00000359971.4 NP_998770.2 Q6ZMY9A0AV05

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF517ENST00000359971.4 linkc.508C>T p.Pro170Ser missense_variant Exon 5 of 5 4 NM_213605.3 ENSP00000353058.3 Q6ZMY9

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
show subpopulations
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
LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1261567685; hg19: chr8-146032809; API