rs7192086

Positions:

• chr16-12967754-T-A
• chr16-12967754-T-C
• chr16-12967754-T-G

Variant summary

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

The NM_001145204.3(SHISA9):​c.691+50939T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 151,898 control chromosomes in the GnomAD database, including 44,654 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 0.77 (44654 hom., cov: 30)
• Consequence: SHISA9 NM_001145204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHISA9	NM_001145204.3	c.691+50939T>A		intron_variant		ENST00000558583.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHISA9	ENST00000558583.3	c.691+50939T>A		intron_variant		5	NM_001145204.3	P1

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116185 AN: 151782 Hom.: 44616 Cov.: 30

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.766 AC: 116278 AN: 151898 Hom.: 44654 Cov.: 30 AF XY: 0.768 AC XY: 56972 AN XY: 74222

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.764

Gnomad4 EAS AF: 0.725

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.758

Alfa AF: 0.755 Hom.: 23719

Bravo AF: 0.768

Asia WGS AF: 0.681 AC: 2368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.8
DANN	Benign	0.86

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: rs7192086; hg19: chr16-13061611;