22-41910497-C-T

Variant names:

• chr22-41910497-C-T
• NM_001207020.3:c.722G>A

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.722G>A​(p.Gly241Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000541 in 1,108,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000054 (0 hom.)
• Consequence: SHISA8 NM_001207020.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.423
• 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=0.14223781).

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.722G>A	p.Gly241Asp	missense	Exon 3 of 4	NP_001193949.1	B8ZZ34-1
	SHISA8	NM_001353438.2		c.1007G>A	p.Gly336Asp	missense	Exon 3 of 4	NP_001340367.1	B8ZZ34-3
	SHISA8	NM_001353439.2		c.899G>A	p.Gly300Asp	missense	Exon 3 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.722G>A	p.Gly241Asp	missense	Exon 3 of 4	ENSP00000481203.1	B8ZZ34-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000541 AC: 6 AN: 1108694 Hom.: 0 Cov.: 31 AF XY: 0.00000376 AC XY: 2 AN XY: 532042

African (AFR) AF: 0.00 AC: 0 AN: 22792

American (AMR) AF: 0.00 AC: 0 AN: 8324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14214

East Asian (EAS) AF: 0.00 AC: 0 AN: 26540

South Asian (SAS) AF: 0.00 AC: 0 AN: 24832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3198

European-Non Finnish (NFE) AF: 0.00000318 AC: 3 AN: 942222

Other (OTH) AF: 0.0000675 AC: 3 AN: 44438

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Benign	0.88
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.14	T
PhyloP100		-0.42
PrimateAI	Uncertain	0.62	T
Sift4G	Benign	0.21	T
Vest4		0.18
MVP		0.31
GERP RS		3.0
Varity_R		0.047
gMVP		0.35

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

hg19: chr22-42306501;