16-13105001-C-T

Variant names:

• chr16-13105001-C-T
• rs251919
• NM_001145204.3:c.692-98393C>T

Variant summary

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

The NM_001145204.3(SHISA9):​c.692-98393C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 151,880 control chromosomes in the GnomAD database, including 3,287 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 (3287 hom., cov: 32)
• Consequence: SHISA9 NM_001145204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISA9	NM_001145204.3	c.692-98393C>T		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.692-98393C>T		intron_variant	Intron 2 of 4	5	NM_001145204.3	ENSP00000454014.2
SHISA9	ENST00000566106.1	n.135+22487C>T		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30159 AN: 151762 Hom.: 3287 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.199 AC: 30170 AN: 151880 Hom.: 3287 Cov.: 32 AF XY: 0.197 AC XY: 14596 AN XY: 74200

African (AFR) AF: 0.123 AC: 5085 AN: 41430

American (AMR) AF: 0.190 AC: 2903 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 545 AN: 3468

East Asian (EAS) AF: 0.218 AC: 1123 AN: 5156

South Asian (SAS) AF: 0.139 AC: 667 AN: 4810

European-Finnish (FIN) AF: 0.249 AC: 2613 AN: 10498

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16594 AN: 67952

Other (OTH) AF: 0.213 AC: 448 AN: 2106

Alfa AF: 0.218 Hom.: 4528

Bravo AF: 0.190

Asia WGS AF: 0.154 AC: 539 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.78
PhyloP100		0.082
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: rs251919; hg19: chr16-13198858;