16-13145040-T-C

Variant names:

• chr16-13145040-T-C
• rs150063
• NM_001145204.3:c.692-58354T>C

Variant summary

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

The NM_001145204.3(SHISA9):​c.692-58354T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 152,124 control chromosomes in the GnomAD database, including 39,038 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 0.70 (39038 hom., cov: 33)
• Consequence: SHISA9 NM_001145204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISA9	NM_001145204.3	c.692-58354T>C		intron_variant	Intron 2 of 4	ENST00000558583.3	NP_001138676.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHISA9	ENST00000558583.3	c.692-58354T>C		intron_variant	Intron 2 of 4	5	NM_001145204.3	ENSP00000454014.2
SHISA9	ENST00000566106.1	n.136-58354T>C		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106832 AN: 152004 Hom.: 39003 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.834

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.703 AC: 106921 AN: 152124 Hom.: 39038 Cov.: 33 AF XY: 0.708 AC XY: 52645 AN XY: 74368

African (AFR) AF: 0.487 AC: 20204 AN: 41462

American (AMR) AF: 0.796 AC: 12168 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2667 AN: 3472

East Asian (EAS) AF: 0.781 AC: 4045 AN: 5178

South Asian (SAS) AF: 0.860 AC: 4139 AN: 4812

European-Finnish (FIN) AF: 0.779 AC: 8255 AN: 10596

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 53029 AN: 68004

Other (OTH) AF: 0.732 AC: 1546 AN: 2112

Alfa AF: 0.762 Hom.: 186612

Bravo AF: 0.693

Asia WGS AF: 0.792 AC: 2752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.4
DANN	Benign	0.68
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs150063; hg19: chr16-13238897;