19-56190079-C-A

Variant summary

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

The NM_001080456.5(ZSCAN5B):​c.1236G>T​(p.Met412Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,752 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M412L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZSCAN5B
NM_001080456.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.77
Variant links:
Genes affected
ZSCAN5B (HGNC:34246): (zinc finger and SCAN domain containing 5B) 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 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=0.018455863).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZSCAN5BNM_001080456.5 linkc.1236G>T p.Met412Ile missense_variant Exon 5 of 5 ENST00000586855.7 NP_001073925.2 A6NJL1
ZSCAN5BNM_001385638.1 linkc.1236G>T p.Met412Ile missense_variant Exon 5 of 5 NP_001372567.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZSCAN5BENST00000586855.7 linkc.1236G>T p.Met412Ile missense_variant Exon 5 of 5 5 NM_001080456.5 ENSP00000466072.2 A6NJL1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000240
AC:
6
AN:
249878
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135530
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000329
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:
1461752
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727164
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000151
ExAC
AF:
0.0000495
AC:
6

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 17, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1236G>T (p.M412I) alteration is located in exon 4 (coding exon 4) of the ZSCAN5B gene. This alteration results from a G to T substitution at nucleotide position 1236, causing the methionine (M) at amino acid position 412 to be replaced by an isoleucine (I). 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
Uncertain
0.38
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.22
DANN
Benign
0.68
DEOGEN2
Benign
0.0052
T;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.074
N
LIST_S2
Benign
0.43
.;T
M_CAP
Benign
0.00061
T
MetaRNN
Benign
0.018
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-0.76
N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.4
.;N
REVEL
Benign
0.010
Sift
Benign
0.10
.;T
Sift4G
Benign
0.11
T;T
Polyphen
0.025
B;B
Vest4
0.10
MutPred
0.33
Loss of disorder (P = 0.0655);Loss of disorder (P = 0.0655);
MVP
0.12
MPC
0.014
ClinPred
0.026
T
GERP RS
-6.3
Varity_R
0.077
gMVP
0.042

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: rs771771953; hg19: chr19-56701448; API