rs10492781

Variant names:

• chr16-13262830-C-T
• rs10492781
• ENST00000571619.5:n.178+4395C>T

Variant summary

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

The ENST00000571619.5(ENSG00000262801):​n.178+4395C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,030 control chromosomes in the GnomAD database, including 2,126 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 0.16 (2126 hom., cov: 31)
• Consequence: ENSG00000262801 ENST00000571619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISA9	XM_047434582.1	c.970+59281C>T		intron_variant	Intron 3 of 4		XP_047290538.1
SHISA9	XM_011522642.3	c.970+59281C>T		intron_variant	Intron 3 of 4		XP_011520944.1
LOC107984137	XR_001752087.2	n.262+4395C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000262801	ENST00000571619.5	n.178+4395C>T		intron_variant	Intron 2 of 4	3
ENSG00000262801	ENST00000574540.2	n.157+16440C>T		intron_variant	Intron 1 of 3	3
ENSG00000262801	ENST00000653029.1	n.159+16440C>T		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23752 AN: 151912 Hom.: 2124 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.0975

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.156 AC: 23757 AN: 152030 Hom.: 2126 Cov.: 31 AF XY: 0.152 AC XY: 11279 AN XY: 74306

African (AFR) AF: 0.113 AC: 4681 AN: 41474

American (AMR) AF: 0.129 AC: 1973 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3462

East Asian (EAS) AF: 0.0162 AC: 84 AN: 5182

South Asian (SAS) AF: 0.0972 AC: 468 AN: 4816

European-Finnish (FIN) AF: 0.154 AC: 1631 AN: 10566

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13665 AN: 67948

Other (OTH) AF: 0.184 AC: 388 AN: 2108

Alfa AF: 0.185 Hom.: 11320

Bravo AF: 0.153

Asia WGS AF: 0.0760 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.34
DANN	Benign	0.64
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs10492781; hg19: chr16-13356687;