chr7-99621431-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_145115.3(ZSCAN25):​c.446A>T​(p.Glu149Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,382,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

ZSCAN25
NM_145115.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42
Variant links:
Genes affected
ZSCAN25 (HGNC:21961): (zinc finger and SCAN domain containing 25) This gene encodes a protein that bears some similarity to zinc finger proteins, which are involved in DNA binding and protein-protein interactions. Multiple alternatively spliced transcript variants have been identified, but the full-length nature for most of them has not been determined. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31564486).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZSCAN25NM_145115.3 linkuse as main transcriptc.446A>T p.Glu149Val missense_variant 5/8 ENST00000394152.7 NP_660090.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZSCAN25ENST00000394152.7 linkuse as main transcriptc.446A>T p.Glu149Val missense_variant 5/85 NM_145115.3 ENSP00000377708 P1Q6NSZ9-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.23e-7
AC:
1
AN:
1382934
Hom.:
0
Cov.:
30
AF XY:
0.00000146
AC XY:
1
AN XY:
685076
show subpopulations
Gnomad4 AFR exome
AF:
0.0000322
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

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 GeneticsApr 25, 2022The c.446A>T (p.E149V) alteration is located in exon 5 (coding exon 2) of the ZSCAN25 gene. This alteration results from a A to T substitution at nucleotide position 446, causing the glutamic acid (E) at amino acid position 149 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
0.26
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
T;T;T
Eigen
Benign
0.13
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.68
.;T;T
M_CAP
Benign
0.0098
T
MetaRNN
Benign
0.32
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;L;.
MutationTaster
Benign
0.77
N;N;N
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-2.1
N;N;.
REVEL
Benign
0.044
Sift
Uncertain
0.0010
D;D;.
Sift4G
Uncertain
0.031
D;D;T
Polyphen
0.43
B;B;.
Vest4
0.55
MutPred
0.35
Loss of disorder (P = 0.0309);Loss of disorder (P = 0.0309);.;
MVP
0.29
MPC
1.0
ClinPred
0.88
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.14
gMVP
0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-99219054; API