22-41909874-C-G

Variant summary

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

The NM_001207020.3(SHISA8):​c.1085G>C​(p.Ser362Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,530,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

SHISA8
NM_001207020.3 missense

Scores

1
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.452
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=0.17259085).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SHISA8NM_001207020.3 linkc.1085G>C p.Ser362Thr missense_variant Exon 4 of 4 ENST00000621082.2 NP_001193949.1
SHISA8NM_001353438.2 linkc.1370G>C p.Ser457Thr missense_variant Exon 4 of 4 NP_001340367.1
SHISA8NM_001353439.2 linkc.1262G>C p.Ser421Thr missense_variant Exon 4 of 4 NP_001340368.1
SHISA8XM_006724256.5 linkc.1250G>C p.Ser417Thr missense_variant Exon 4 of 4 XP_006724319.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SHISA8ENST00000621082.2 linkc.1085G>C p.Ser362Thr missense_variant Exon 4 of 4 5 NM_001207020.3 ENSP00000481203.1 B8ZZ34-1

Frequencies

GnomAD3 genomes
AF:
0.0000985
AC:
15
AN:
152220
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000338
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000809
AC:
1
AN:
123590
Hom.:
0
AF XY:
0.0000148
AC XY:
1
AN XY:
67720
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000429
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:
0.00000653
AC:
9
AN:
1378272
Hom.:
0
Cov.:
31
AF XY:
0.00000147
AC XY:
1
AN XY:
679942
show subpopulations
Gnomad4 AFR exome
AF:
0.000289
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
AF:
0.0000985
AC:
15
AN:
152220
Hom.:
0
Cov.:
33
AF XY:
0.000134
AC XY:
10
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.000338
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.000106

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1085G>C (p.S362T) alteration is located in exon 4 (coding exon 4) of the SHISA8 gene. This alteration results from a G to C substitution at nucleotide position 1085, causing the serine (S) at amino acid position 362 to be replaced by a threonine (T). 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
-0.39
T
BayesDel_noAF
Benign
-0.44
CADD
Uncertain
24
DANN
Benign
0.60
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.17
T
MetaRNN
Benign
0.17
T
PrimateAI
Pathogenic
0.81
D
Sift4G
Benign
0.10
T
Vest4
0.19
MVP
0.39
GERP RS
4.1
Varity_R
0.15
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1002539169; hg19: chr22-42305878; API