rs204034

Positions:

• chr16-13229484-A-G
• chr16-13229484-A-T

Variant summary

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

The NM_001145204.3(SHISA9):​c.896-5546A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,120 control chromosomes in the GnomAD database, including 51,033 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 0.82 (51033 hom., cov: 31)
• Consequence: SHISA9 NM_001145204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.383

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHISA9	NM_001145204.3	c.896-5546A>G		intron_variant		ENST00000558583.3	NP_001138676.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHISA9	ENST00000558583.3	c.896-5546A>G		intron_variant		5	NM_001145204.3	ENSP00000454014	P1
SHISA9	ENST00000566106.1	n.292-5546A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124366 AN: 152002 Hom.: 50990 Cov.: 31

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.793

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.836

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

GnomAD4 genome AF: 0.818 AC: 124467 AN: 152120 Hom.: 51033 Cov.: 31 AF XY: 0.822 AC XY: 61088 AN XY: 74356

Gnomad4 AFR AF: 0.831

Gnomad4 AMR AF: 0.864

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.801

Gnomad4 FIN AF: 0.794

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.838

Alfa AF: 0.808 Hom.: 66535

Bravo AF: 0.826

Asia WGS AF: 0.863 AC: 3000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.43
DANN	Benign	0.42

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: rs204034; hg19: chr16-13323341;