rs149228

Positions:

• chr16-13210617-A-C
• chr16-13210617-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145204.3(SHISA9):​c.848-2636A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,088 control chromosomes in the GnomAD database, including 3,341 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 0.20 (3341 hom., cov: 32)
• Consequence: SHISA9 NM_001145204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHISA9	NM_001145204.3	c.848-2636A>C		intron_variant		ENST00000558583.3	NP_001138676.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHISA9	ENST00000558583.3	c.848-2636A>C		intron_variant		5	NM_001145204.3	ENSP00000454014	P1
SHISA9	ENST00000566106.1	n.291+7068A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30547 AN: 151970 Hom.: 3335 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.201 AC: 30566 AN: 152088 Hom.: 3341 Cov.: 32 AF XY: 0.206 AC XY: 15316 AN XY: 74328

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.213

Alfa AF: 0.197 Hom.: 3969

Bravo AF: 0.203

Asia WGS AF: 0.376 AC: 1303 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.78
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs149228; hg19: chr16-13304474;