19-7519495-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018083.5(ZNF358):​c.253C>T​(p.Pro85Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ZNF358
NM_018083.5 missense

Scores

1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.537
Variant links:
Genes affected
ZNF358 (HGNC:16838): (zinc finger protein 358) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in several processes, including embryonic forelimb morphogenesis; neural tube development; and stem cell population maintenance. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.056527913).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF358NM_018083.5 linkuse as main transcriptc.253C>T p.Pro85Ser missense_variant 2/2 ENST00000597229.2 NP_060553.4 Q9NW07

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF358ENST00000597229.2 linkuse as main transcriptc.253C>T p.Pro85Ser missense_variant 2/22 NM_018083.5 ENSP00000472305.1 Q9NW07
ENSG00000267952ENST00000599312.1 linkuse as main transcriptc.*207C>T 3_prime_UTR_variant 2/22 ENSP00000469588.1 M0QY47
ZNF358ENST00000596712.1 linkuse as main transcriptc.253C>T p.Pro85Ser missense_variant 2/23 ENSP00000472777.1 M0R2S5
ENSG00000267952ENST00000597384.1 linkuse as main transcriptn.507C>T non_coding_transcript_exon_variant 3/33

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000240
AC:
6
AN:
249886
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135266
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461250
Hom.:
0
Cov.:
42
AF XY:
0.00000550
AC XY:
4
AN XY:
726940
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000201
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 15, 2022The c.253C>T (p.P85S) alteration is located in exon 2 (coding exon 1) of the ZNF358 gene. This alteration results from a C to T substitution at nucleotide position 253, causing the proline (P) at amino acid position 85 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
0.077
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
9.7
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0018
.;T
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.55
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.77
T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.057
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
.;N
PrimateAI
Benign
0.45
T
Sift4G
Benign
0.099
T;T
Polyphen
0.089
.;B
Vest4
0.070
MutPred
0.38
Gain of phosphorylation at P85 (P = 0.0025);Gain of phosphorylation at P85 (P = 0.0025);
MVP
0.19
ClinPred
0.035
T
GERP RS
3.1
Varity_R
0.029
gMVP
0.21

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: rs769064740; hg19: chr19-7584381; API