22-41909827-C-T

Variant names:

• chr22-41909827-C-T
• rs2077534934
• NM_001207020.3:c.1132G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001207020.3(SHISA8):​c.1132G>A​(p.Gly378Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,369,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G378R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: SHISA8 NM_001207020.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055993766).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001207020.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHISA8	NM_001207020.3	MANE Select	c.1132G>A	p.Gly378Ser	missense	Exon 4 of 4	NP_001193949.1	B8ZZ34-1
	SHISA8	NM_001353438.2		c.1417G>A	p.Gly473Ser	missense	Exon 4 of 4	NP_001340367.1	B8ZZ34-3
	SHISA8	NM_001353439.2		c.1309G>A	p.Gly437Ser	missense	Exon 4 of 4	NP_001340368.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHISA8	ENST00000621082.2	TSL:5 MANE Select	c.1132G>A	p.Gly378Ser	missense	Exon 4 of 4	ENSP00000481203.1	B8ZZ34-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1369830 Hom.: 0 Cov.: 31 AF XY: 0.00000296 AC XY: 2 AN XY: 675558

African (AFR) AF: 0.00 AC: 0 AN: 30410

American (AMR) AF: 0.00 AC: 0 AN: 34044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24854

East Asian (EAS) AF: 0.00 AC: 0 AN: 34286

South Asian (SAS) AF: 0.00 AC: 0 AN: 77138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5638

European-Non Finnish (NFE) AF: 9.32e-7 AC: 1 AN: 1072702

Other (OTH) AF: 0.0000174 AC: 1 AN: 57388

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.3
DANN	Benign	0.92
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.056	T
PhyloP100		-0.81
PrimateAI	Benign	0.48	T
Sift4G	Benign	0.79	T
Vest4		0.085
MVP		0.11
GERP RS		-7.6
Varity_R		0.041
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2077534934; hg19: chr22-42305831;