22-41910053-C-T

Variant names:

• chr22-41910053-C-T
• rs1020459397
• NM_001207020.3:c.906G>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.906G>A​(p.Leu302Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000907 in 1,103,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: SHISA8 NM_001207020.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• 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 (BayesDel_noAF=-0.59).

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.906G>A	p.Leu302Leu	synonymous	Exon 4 of 4	NP_001193949.1	B8ZZ34-1
	SHISA8	NM_001353438.2		c.1191G>A	p.Leu397Leu	synonymous	Exon 4 of 4	NP_001340367.1	B8ZZ34-3
	SHISA8	NM_001353439.2		c.1083G>A	p.Leu361Leu	synonymous	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.906G>A	p.Leu302Leu	synonymous	Exon 4 of 4	ENSP00000481203.1	B8ZZ34-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.07e-7 AC: 1 AN: 1103092 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 523660

African (AFR) AF: 0.00 AC: 0 AN: 22728

American (AMR) AF: 0.00 AC: 0 AN: 8262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14412

East Asian (EAS) AF: 0.00 AC: 0 AN: 26184

South Asian (SAS) AF: 0.00 AC: 0 AN: 23854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3006

European-Non Finnish (NFE) AF: 0.00000107 AC: 1 AN: 937166

Other (OTH) AF: 0.00 AC: 0 AN: 44814

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.3
DANN	Benign	0.88
PhyloP100		1.2

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

Other links and lift over

dbSNP: rs1020459397; hg19: chr22-42306057;