chr19-58335017-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181846.3(ZSCAN22):​c.215C>T​(p.Ala72Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000524 in 1,614,002 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: 𝑓 0.00040 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00054 ( 0 hom. )

Consequence

ZSCAN22
NM_181846.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.315
Variant links:
Genes affected
ZSCAN22 (HGNC:4929): (zinc finger and SCAN domain containing 22) 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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07371491).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZSCAN22NM_181846.3 linkc.215C>T p.Ala72Val missense_variant Exon 2 of 3 ENST00000329665.5 NP_862829.1 P10073

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZSCAN22ENST00000329665.5 linkc.215C>T p.Ala72Val missense_variant Exon 2 of 3 1 NM_181846.3 ENSP00000332433.3 P10073

Frequencies

GnomAD3 genomes
AF:
0.000401
AC:
61
AN:
152240
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000723
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000916
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000632
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000342
AC:
86
AN:
251100
Hom.:
0
AF XY:
0.000361
AC XY:
49
AN XY:
135774
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.000528
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000537
AC:
785
AN:
1461762
Hom.:
0
Cov.:
30
AF XY:
0.000525
AC XY:
382
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.000537
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.000643
Gnomad4 OTH exome
AF:
0.000646
GnomAD4 genome
AF:
0.000401
AC:
61
AN:
152240
Hom.:
0
Cov.:
33
AF XY:
0.000363
AC XY:
27
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.0000723
Gnomad4 AMR
AF:
0.000916
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000632
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000295
Hom.:
0
Bravo
AF:
0.000446
TwinsUK
AF:
0.000809
AC:
3
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000321
AC:
39
EpiCase
AF:
0.000218
EpiControl
AF:
0.000474

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.215C>T (p.A72V) alteration is located in exon 2 (coding exon 1) of the ZSCAN22 gene. This alteration results from a C to T substitution at nucleotide position 215, causing the alanine (A) at amino acid position 72 to be replaced by a valine (V). 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
0.21
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.82
CADD
Benign
12
DANN
Benign
0.95
DEOGEN2
Benign
0.028
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.013
N
LIST_S2
Benign
0.36
T
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.074
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-0.060
N
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-0.98
N
REVEL
Benign
0.025
Sift
Uncertain
0.0040
D
Sift4G
Benign
0.18
T
Polyphen
0.0020
B
Vest4
0.21
MVP
0.15
MPC
0.11
ClinPred
0.019
T
GERP RS
-0.87
Varity_R
0.071
gMVP
0.066

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: rs139579517; hg19: chr19-58846383; COSMIC: COSV61639249; COSMIC: COSV61639249; API