ENST00000571619.5:n.420+46102A>C

Variant names:

• chr16-13396523-A-C
• rs734826
• ENST00000571619.5:n.420+46102A>C

Variant summary

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

The ENST00000571619.5(ENSG00000262801):​n.420+46102A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 152,012 control chromosomes in the GnomAD database, including 32,557 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 0.65 (32557 hom., cov: 32)
• Consequence: ENSG00000262801 ENST00000571619.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• Publications: 7 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISA9	XM_047434582.1	c.1212+46102A>C		intron_variant	Intron 4 of 4		XP_047290538.1
SHISA9	XM_011522642.3	c.1212+46102A>C		intron_variant	Intron 4 of 4		XP_011520944.1
SHISA9	XR_007064905.1	n.1556+46102A>C		intron_variant	Intron 4 of 6
SHISA9	XR_932915.3	n.1556+46102A>C		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000262801	ENST00000571619.5	n.420+46102A>C		intron_variant	Intron 3 of 4	3
ENSG00000262801	ENST00000574540.2	n.594+45907A>C		intron_variant	Intron 2 of 3	3
ENSG00000262801	ENST00000653029.1	n.401+46102A>C		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98145 AN: 151894 Hom.: 32510 Cov.: 32

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.646 AC: 98244 AN: 152012 Hom.: 32557 Cov.: 32 AF XY: 0.639 AC XY: 47484 AN XY: 74272

African (AFR) AF: 0.795 AC: 32967 AN: 41478

American (AMR) AF: 0.531 AC: 8098 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2307 AN: 3472

East Asian (EAS) AF: 0.616 AC: 3175 AN: 5152

South Asian (SAS) AF: 0.691 AC: 3330 AN: 4818

European-Finnish (FIN) AF: 0.533 AC: 5628 AN: 10552

Middle Eastern (MID) AF: 0.712 AC: 208 AN: 292

European-Non Finnish (NFE) AF: 0.597 AC: 40554 AN: 67974

Other (OTH) AF: 0.634 AC: 1340 AN: 2112

Alfa AF: 0.603 Hom.: 46733

Bravo AF: 0.648

Asia WGS AF: 0.684 AC: 2378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		-0.64

Splicing

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

Other links and lift over

dbSNP: rs734826; hg19: chr16-13490380;