rs4465599

Variant names:

• chr16-13061021-G-A
• rs4465599
• NM_001145204.3:c.692-142373G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145204.3(SHISA9):​c.692-142373G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 151,998 control chromosomes in the GnomAD database, including 36,753 homozygotes. 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: 𝑓 0.69 (36753 hom., cov: 32)
• Consequence: SHISA9 NM_001145204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.879
• Publications: 5 publications found

Genes affected

SHISA9 (HGNC:37231): (shisa family member 9) Predicted to enable PDZ domain binding activity. Predicted to be involved in regulation of AMPA receptor activity and regulation of short-term neuronal synaptic plasticity. Predicted to be located in synapse. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in glutamatergic synapse; postsynaptic density; and synaptic membrane. Predicted to be integral component of postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISA9	NM_001145204.3	c.692-142373G>A		intron_variant	Intron 2 of 4	ENST00000558583.3	NP_001138676.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHISA9	ENST00000558583.3	c.692-142373G>A		intron_variant	Intron 2 of 4	5	NM_001145204.3	ENSP00000454014.2

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105095 AN: 151880 Hom.: 36757 Cov.: 32

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.729

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.692 AC: 105139 AN: 151998 Hom.: 36753 Cov.: 32 AF XY: 0.694 AC XY: 51530 AN XY: 74260

African (AFR) AF: 0.570 AC: 23603 AN: 41438

American (AMR) AF: 0.727 AC: 11115 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2614 AN: 3466

East Asian (EAS) AF: 0.780 AC: 4021 AN: 5156

South Asian (SAS) AF: 0.698 AC: 3365 AN: 4820

European-Finnish (FIN) AF: 0.777 AC: 8189 AN: 10540

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.732 AC: 49733 AN: 67974

Other (OTH) AF: 0.728 AC: 1537 AN: 2110

Alfa AF: 0.714 Hom.: 65988

Bravo AF: 0.685

Asia WGS AF: 0.746 AC: 2594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.53
PhyloP100		0.88
Mutation Taster		=100/0	polymorphism (auto)

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: rs4465599; hg19: chr16-13154878;