rs10492775

Variant names:

• chr16-13527425-T-C
• rs10492775
• ENST00000571619.5:n.553-35282T>C

Variant summary

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

The ENST00000571619.5(ENSG00000262801):​n.553-35282T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0822 in 152,192 control chromosomes in the GnomAD database, including 574 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 0.082 (574 hom., cov: 32)
• Consequence: ENSG00000262801 ENST00000571619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291
• Publications: 1 publications found

Genes affected

ENSG00000262801 (HGNC:):

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISA9	XR_007064905.1	n.1689-24968T>C		intron_variant	Intron 5 of 6
SHISA9	XR_932915.3	n.1689-35282T>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000262801	ENST00000571619.5	n.553-35282T>C		intron_variant	Intron 4 of 4	3
ENSG00000262801	ENST00000574540.2	n.727-35282T>C		intron_variant	Intron 3 of 3	3
ENSG00000262801	ENST00000653029.1	n.534-24968T>C		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.0822 AC: 12498 AN: 152074 Hom.: 572 Cov.: 32

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0933

Gnomad FIN AF: 0.0517

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0794

Gnomad OTH AF: 0.0975

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

GnomAD4 genome AF: 0.0822 AC: 12509 AN: 152192 Hom.: 574 Cov.: 32 AF XY: 0.0838 AC XY: 6237 AN XY: 74398

African (AFR) AF: 0.0549 AC: 2279 AN: 41548

American (AMR) AF: 0.162 AC: 2472 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 250 AN: 3472

East Asian (EAS) AF: 0.156 AC: 805 AN: 5176

South Asian (SAS) AF: 0.0934 AC: 449 AN: 4806

European-Finnish (FIN) AF: 0.0517 AC: 548 AN: 10606

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0795 AC: 5403 AN: 67998

Other (OTH) AF: 0.0960 AC: 203 AN: 2114

Alfa AF: 0.0819 Hom.: 65

Bravo AF: 0.0901

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.32
PhyloP100		0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10492775; hg19: chr16-13621282;