chr3-48469373-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016479.6(SHISA5):​c.631G>A​(p.Glu211Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000101 in 1,587,668 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SHISA5
NM_016479.6 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78
Variant links:
Genes affected
SHISA5 (HGNC:30376): (shisa family member 5) This gene encodes a member of the shisa family. The encoded protein is localized to the endoplasmic reticulum, and together with p53 induces apoptosis in a caspase-dependent manner. Alternative splicing results in multiple transcript variants. Related pseudogenes of this gene are found on chromosome X. [provided by RefSeq, Apr 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SHISA5NM_016479.6 linkc.631G>A p.Glu211Lys missense_variant Exon 5 of 6 ENST00000296444.7 NP_057563.3 Q8N114-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SHISA5ENST00000296444.7 linkc.631G>A p.Glu211Lys missense_variant Exon 5 of 6 1 NM_016479.6 ENSP00000296444.2 Q8N114-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152032
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000129
AC:
3
AN:
232878
Hom.:
0
AF XY:
0.00000800
AC XY:
1
AN XY:
124992
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000921
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000104
AC:
15
AN:
1435636
Hom.:
0
Cov.:
31
AF XY:
0.0000127
AC XY:
9
AN XY:
710550
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000935
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:
0.00000730
Gnomad4 OTH exome
AF:
0.0000507
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152032
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74248
show subpopulations
Gnomad4 AFR
AF:
0.0000242
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.631G>A (p.E211K) alteration is located in exon 5 (coding exon 5) of the SHISA5 gene. This alteration results from a G to A substitution at nucleotide position 631, causing the glutamic acid (E) at amino acid position 211 to be replaced by a lysine (K). 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
0.47
BayesDel_addAF
Benign
-0.072
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
.;T;.;.;.;.
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.85
D;D;.;D;.;D
M_CAP
Benign
0.058
D
MetaRNN
Uncertain
0.70
D;D;D;D;D;D
MetaSVM
Benign
-0.62
T
MutationAssessor
Benign
2.0
.;M;.;.;.;.
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-1.8
.;N;N;N;N;N
REVEL
Benign
0.14
Sift
Uncertain
0.010
.;D;D;D;D;D
Sift4G
Benign
0.13
T;T;T;T;T;T
Polyphen
1.0, 1.0
.;D;.;D;.;.
Vest4
0.79
MutPred
0.19
.;Gain of methylation at E211 (P = 0.0026);.;.;.;.;
MVP
0.49
MPC
0.43
ClinPred
0.86
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.16
gMVP
0.39

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: rs1381357840; hg19: chr3-48510772; API