1-33489593-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001377376.1(ZSCAN20):​c.757G>A​(p.Val253Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000169 in 1,613,948 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 2 hom. )

Consequence

ZSCAN20
NM_001377376.1 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.62
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.005859971).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZSCAN20NM_001377376.1 linkc.757G>A p.Val253Met missense_variant 5/8 ENST00000684572.1 NP_001364305.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZSCAN20ENST00000684572.1 linkc.757G>A p.Val253Met missense_variant 5/8 NM_001377376.1 ENSP00000507139.1 P17040-1
ZSCAN20ENST00000373413.2 linkc.604+942G>A intron_variant 1 ENSP00000362512.1 P17040-4
ZSCAN20ENST00000361328.7 linkc.757G>A p.Val253Met missense_variant 5/82 ENSP00000355053.3 P17040-1

Frequencies

GnomAD3 genomes
AF:
0.000184
AC:
28
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00519
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000309
AC:
77
AN:
249368
Hom.:
1
AF XY:
0.000273
AC XY:
37
AN XY:
135302
show subpopulations
Gnomad AFR exome
AF:
0.000129
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00666
Gnomad EAS exome
AF:
0.0000556
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000530
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000168
AC:
245
AN:
1461786
Hom.:
2
Cov.:
31
AF XY:
0.000164
AC XY:
119
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00712
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000315
Gnomad4 OTH exome
AF:
0.000348
GnomAD4 genome
AF:
0.000184
AC:
28
AN:
152162
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00519
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000373
Hom.:
1
Bravo
AF:
0.000204
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000121
AC:
1
ExAC
AF:
0.000190
AC:
23
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000237

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 21, 2023The c.757G>A (p.V253M) alteration is located in exon 5 (coding exon 4) of the ZSCAN20 gene. This alteration results from a G to A substitution at nucleotide position 757, causing the valine (V) at amino acid position 253 to be replaced by a methionine (M). 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
0.11
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
0.63
DANN
Benign
0.92
DEOGEN2
Benign
0.030
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.013
N
LIST_S2
Benign
0.67
T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.0059
T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
1.2
L
PrimateAI
Benign
0.27
T
REVEL
Benign
0.083
Sift4G
Uncertain
0.057
T
Polyphen
0.016
B
Vest4
0.23
MVP
0.061
MPC
0.22
ClinPred
0.020
T
GERP RS
-8.3
Varity_R
0.028
gMVP
0.063

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: rs201693798; hg19: chr1-33955193; API