chr22-41910053-C-A

Variant names:

• chr22-41910053-C-A
• NM_001207020.3:c.906G>T
• SHISA8 p.Leu302Phe

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001207020.3(SHISA8):​c.906G>T​(p.Leu302Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 8/12 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SHISA8 NM_001207020.3 missense
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14173645).

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>T	p.Leu302Phe	missense	Exon 4 of 4	NP_001193949.1	B8ZZ34-1
	SHISA8	NM_001353438.2		c.1191G>T	p.Leu397Phe	missense	Exon 4 of 4	NP_001340367.1	B8ZZ34-3
	SHISA8	NM_001353439.2		c.1083G>T	p.Leu361Phe	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.906G>T	p.Leu302Phe	missense	Exon 4 of 4	ENSP00000481203.1	B8ZZ34-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Benign	0.68
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.14	T
PhyloP100		1.2
PrimateAI	Pathogenic	0.86	D
Sift4G	Uncertain	0.041	D
Varity_R		0.055
gMVP		0.17

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-42306057;