16-13107581-G-A

Position:

• chr16-13107581-G-A

Variant summary

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

The NM_001145204.3(SHISA9):​c.692-95813G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 151,538 control chromosomes in the GnomAD database, including 3,351 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 (3351 hom., cov: 31)
• Consequence: SHISA9 NM_001145204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHISA9	NM_001145204.3	c.692-95813G>A		intron_variant		ENST00000558583.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHISA9	ENST00000558583.3	c.692-95813G>A		intron_variant		5	NM_001145204.3	P1
SHISA9	ENST00000566106.1	n.135+25067G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30040 AN: 151420 Hom.: 3351 Cov.: 31

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.198 AC: 30042 AN: 151538 Hom.: 3351 Cov.: 31 AF XY: 0.196 AC XY: 14500 AN XY: 73990

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.212

Alfa AF: 0.210 Hom.: 533

Bravo AF: 0.188

Asia WGS AF: 0.156 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.75

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: rs1230895; hg19: chr16-13201438;