rs928333420

Variant names:

• chr22-41909950-C-T
• rs928333420
• NM_001207020.3:c.1009G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001207020.3(SHISA8):​c.1009G>A​(p.Ala337Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000379 in 1,476,514 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: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: SHISA8 NM_001207020.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.149
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012098044).

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.1009G>A	p.Ala337Thr	missense	Exon 4 of 4	NP_001193949.1	B8ZZ34-1
	SHISA8	NM_001353438.2		c.1294G>A	p.Ala432Thr	missense	Exon 4 of 4	NP_001340367.1	B8ZZ34-3
	SHISA8	NM_001353439.2		c.1186G>A	p.Ala396Thr	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.1009G>A	p.Ala337Thr	missense	Exon 4 of 4	ENSP00000481203.1	B8ZZ34-1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152012 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000774

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000237 AC: 19 AN: 80036 AF XY: 0.000265

Gnomad AFR exome AF: 0.000546

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00387

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000385 AC: 51 AN: 1324502 Hom.: 0 Cov.: 31 AF XY: 0.0000445 AC XY: 29 AN XY: 652038

African (AFR) AF: 0.0000366 AC: 1 AN: 27334

American (AMR) AF: 0.00 AC: 0 AN: 27092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22784

East Asian (EAS) AF: 0.00156 AC: 48 AN: 30800

South Asian (SAS) AF: 0.00 AC: 0 AN: 71386

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4468

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1052880

Other (OTH) AF: 0.0000363 AC: 2 AN: 55130

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152012 Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4 AN XY: 74260

African (AFR) AF: 0.00 AC: 0 AN: 41414

American (AMR) AF: 0.0000655 AC: 1 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000642

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	0.076
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.3
DANN	Benign	0.88
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.012	T
PhyloP100		-0.15
PrimateAI	Uncertain	0.77	T
Sift4G	Benign	0.72	T
Vest4		0.067
MVP		0.18
GERP RS		-2.4
Varity_R		0.021
gMVP		0.15

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: rs928333420; hg19: chr22-42305954;