1-33479437-C-G

Variant summary

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

The NM_001377376.1(ZSCAN20):ā€‹c.149C>Gā€‹(p.Ser50Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,112 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

ZSCAN20
NM_001377376.1 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01
Variant links:
Genes affected
ZSCAN20 (HGNC:13093): (zinc finger and SCAN domain containing 20) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. 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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZSCAN20NM_001377376.1 linkuse as main transcriptc.149C>G p.Ser50Cys missense_variant 2/8 ENST00000684572.1 NP_001364305.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZSCAN20ENST00000684572.1 linkuse as main transcriptc.149C>G p.Ser50Cys missense_variant 2/8 NM_001377376.1 ENSP00000507139 P1P17040-1
ZSCAN20ENST00000373413.2 linkuse as main transcriptc.149C>G p.Ser50Cys missense_variant 2/41 ENSP00000362512 P17040-4
ZSCAN20ENST00000361328.7 linkuse as main transcriptc.149C>G p.Ser50Cys missense_variant 2/82 ENSP00000355053 P1P17040-1
ZSCAN20ENST00000480917.1 linkuse as main transcriptn.291C>G non_coding_transcript_exon_variant 2/43

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152246
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000723
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249202
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135262
show subpopulations
Gnomad AFR exome
AF:
0.0000648
Gnomad AMR exome
AF:
0.00
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:
0.00000137
AC:
2
AN:
1461866
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727232
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152246
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.0000723
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302

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 GeneticsMar 01, 2024The c.149C>G (p.S50C) alteration is located in exon 2 (coding exon 1) of the ZSCAN20 gene. This alteration results from a C to G substitution at nucleotide position 149, causing the serine (S) at amino acid position 50 to be replaced by a cysteine (C). 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
0.19
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.048
T;.
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.68
T;T
M_CAP
Benign
0.0073
T
MetaRNN
Uncertain
0.56
D;D
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-0.32
N;N
MutationTaster
Benign
0.83
D;D;D
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.47
.;N
REVEL
Benign
0.20
Sift
Benign
0.054
.;T
Sift4G
Uncertain
0.036
D;D
Polyphen
1.0
D;D
Vest4
0.66
MutPred
0.44
Loss of disorder (P = 0.0084);Loss of disorder (P = 0.0084);
MVP
0.30
MPC
0.79
ClinPred
0.25
T
GERP RS
5.1
Varity_R
0.091
gMVP
0.57

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: rs1046586930; hg19: chr1-33945038; API