chr7-100057398-G-C

Variant summary

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

The ENST00000292450.9(ZSCAN21):ā€‹c.392G>Cā€‹(p.Gly131Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000647 in 1,546,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G131R) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000057 ( 0 hom. )

Consequence

ZSCAN21
ENST00000292450.9 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.115
Variant links:
Genes affected
ZSCAN21 (HGNC:13104): (zinc finger and SCAN domain containing 21) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive 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 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=0.045948714).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZSCAN21NM_145914.3 linkuse as main transcriptc.392G>C p.Gly131Ala missense_variant 2/4 ENST00000292450.9 NP_666019.1 Q9Y5A6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZSCAN21ENST00000292450.9 linkuse as main transcriptc.392G>C p.Gly131Ala missense_variant 2/41 NM_145914.3 ENSP00000292450.4 Q9Y5A6
ZSCAN21ENST00000456748.6 linkuse as main transcriptc.392G>C p.Gly131Ala missense_variant 2/55 ENSP00000390960.2 G3V0F4
ZSCAN21ENST00000438937.1 linkuse as main transcriptc.392G>C p.Gly131Ala missense_variant 3/42 ENSP00000404207.1 C9JHD9
ZSCAN21ENST00000477297.1 linkuse as main transcriptn.488G>C non_coding_transcript_exon_variant 1/33

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152230
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000216
AC:
4
AN:
185098
Hom.:
0
AF XY:
0.0000404
AC XY:
4
AN XY:
99086
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000459
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000574
AC:
8
AN:
1394224
Hom.:
0
Cov.:
31
AF XY:
0.00000582
AC XY:
4
AN XY:
687070
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:
0.00000740
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152230
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ExAC
AF:
0.0000165
AC:
2

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 GeneticsJun 03, 2024The c.392G>C (p.G131A) alteration is located in exon 2 (coding exon 1) of the ZSCAN21 gene. This alteration results from a G to C substitution at nucleotide position 392, causing the glycine (G) at amino acid position 131 to be replaced by an alanine (A). 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
0.12
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
11
DANN
Benign
0.48
DEOGEN2
Benign
0.22
T;T;T;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.096
N
LIST_S2
Benign
0.17
T;T;T;T
M_CAP
Benign
0.0037
T
MetaRNN
Benign
0.046
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.3
M;.;.;.
MutationTaster
Benign
0.91
N;N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-2.3
N;D;D;.
REVEL
Benign
0.064
Sift
Benign
0.28
T;T;T;.
Sift4G
Benign
0.24
T;T;T;T
Polyphen
0.0060
B;.;.;.
Vest4
0.037
MutPred
0.45
Gain of phosphorylation at T136 (P = 0.2585);Gain of phosphorylation at T136 (P = 0.2585);Gain of phosphorylation at T136 (P = 0.2585);.;
MVP
0.16
MPC
0.13
ClinPred
0.046
T
GERP RS
-0.33
Varity_R
0.074
gMVP
0.19

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: rs747285309; hg19: chr7-99655021; API