16-13124048-A-G

Variant names:

• chr16-13124048-A-G
• rs4781415
• NM_001145204.3:c.692-79346A>G

Variant summary

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

The NM_001145204.3(SHISA9):​c.692-79346A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,062 control chromosomes in the GnomAD database, including 17,373 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 0.44 (17373 hom., cov: 32)
• Consequence: SHISA9 NM_001145204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.752
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISA9	NM_001145204.3	c.692-79346A>G		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.692-79346A>G		intron_variant	Intron 2 of 4	5	NM_001145204.3	ENSP00000454014.2
SHISA9	ENST00000566106.1	n.135+41534A>G		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67633 AN: 151944 Hom.: 17373 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.445 AC: 67648 AN: 152062 Hom.: 17373 Cov.: 32 AF XY: 0.446 AC XY: 33185 AN XY: 74328

African (AFR) AF: 0.176 AC: 7301 AN: 41500

American (AMR) AF: 0.510 AC: 7800 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1958 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2448 AN: 5154

South Asian (SAS) AF: 0.453 AC: 2181 AN: 4816

European-Finnish (FIN) AF: 0.601 AC: 6346 AN: 10558

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 38022 AN: 67964

Other (OTH) AF: 0.479 AC: 1011 AN: 2112

Alfa AF: 0.529 Hom.: 29721

Bravo AF: 0.427

Asia WGS AF: 0.419 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.61
DANN	Benign	0.40
PhyloP100		-0.75
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: rs4781415; hg19: chr16-13217905;