22-41910426-C-A

Variant summary

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

The NM_001207020.3(SHISA8):​c.793G>T​(p.Ala265Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000083 in 1,205,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 8.3e-7 ( 0 hom. )

Consequence

SHISA8
NM_001207020.3 missense

Scores

1
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.105
Variant links:
Genes affected
SHISA8 (HGNC:18351): (shisa family member 8) Predicted to be involved in regulation of AMPA receptor activity and regulation of short-term neuronal synaptic plasticity. Predicted to be integral component of membrane. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in dendritic spine membrane; postsynaptic density; and postsynaptic membrane. [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=0.17876405).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SHISA8NM_001207020.3 linkc.793G>T p.Ala265Ser missense_variant Exon 3 of 4 ENST00000621082.2 NP_001193949.1
SHISA8NM_001353438.2 linkc.1078G>T p.Ala360Ser missense_variant Exon 3 of 4 NP_001340367.1
SHISA8NM_001353439.2 linkc.970G>T p.Ala324Ser missense_variant Exon 3 of 4 NP_001340368.1
SHISA8XM_006724256.5 linkc.958G>T p.Ala320Ser missense_variant Exon 3 of 4 XP_006724319.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SHISA8ENST00000621082.2 linkc.793G>T p.Ala265Ser missense_variant Exon 3 of 4 5 NM_001207020.3 ENSP00000481203.1 B8ZZ34-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
8.30e-7
AC:
1
AN:
1205130
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
589982
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:
0.00000101
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 14, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.793G>T (p.A265S) alteration is located in exon 3 (coding exon 3) of the SHISA8 gene. This alteration results from a G to T substitution at nucleotide position 793, causing the alanine (A) at amino acid position 265 to be replaced by a serine (S). 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
0.10
BayesDel_addAF
Benign
-0.050
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
19
DANN
Benign
0.78
FATHMM_MKL
Benign
0.093
N
LIST_S2
Benign
0.49
T
MetaRNN
Benign
0.18
T
PrimateAI
Uncertain
0.74
T
Sift4G
Benign
0.17
T
Vest4
0.31
MVP
0.18
GERP RS
2.2
Varity_R
0.052
gMVP
0.42

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: chr22-42306430; API