chr22-41909789-A-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001207020.3(SHISA8):āc.1170T>Gā(p.Asn390Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000134 in 1,495,434 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Exomes š: 7.4e-7 ( 0 hom. )
Consequence
SHISA8
NM_001207020.3 missense
NM_001207020.3 missense
Scores
2
3
4
Clinical Significance
Conservation
PhyloP100: 4.62
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHISA8 | NM_001207020.3 | c.1170T>G | p.Asn390Lys | missense_variant | 4/4 | ENST00000621082.2 | |
SHISA8 | NM_001353438.2 | c.1455T>G | p.Asn485Lys | missense_variant | 4/4 | ||
SHISA8 | NM_001353439.2 | c.1347T>G | p.Asn449Lys | missense_variant | 4/4 | ||
SHISA8 | XM_006724256.5 | c.1335T>G | p.Asn445Lys | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHISA8 | ENST00000621082.2 | c.1170T>G | p.Asn390Lys | missense_variant | 4/4 | 5 | NM_001207020.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
1
AN:
152182
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000102 AC: 1AN: 97598Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 54514
GnomAD3 exomes
AF:
AC:
1
AN:
97598
Hom.:
AF XY:
AC XY:
0
AN XY:
54514
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 7.44e-7 AC: 1AN: 1343252Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 661868
GnomAD4 exome
AF:
AC:
1
AN:
1343252
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
661868
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74342
GnomAD4 genome
AF:
AC:
1
AN:
152182
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74342
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
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 submitter | clinical testing | Ambry Genetics | Dec 15, 2023 | The c.1170T>G (p.N390K) alteration is located in exon 4 (coding exon 4) of the SHISA8 gene. This alteration results from a T to G substitution at nucleotide position 1170, causing the asparagine (N) at amino acid position 390 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
MetaRNN
Uncertain
D
PrimateAI
Uncertain
T
Sift4G
Pathogenic
D
Vest4
MVP
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at