rs12602611

Variant names:

• chr17-11337105-G-A
• rs12602611
• NM_207386.4:c.800-42309G>A

Variant summary

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

The NM_207386.4(SHISA6):​c.800-42309G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,070 control chromosomes in the GnomAD database, including 3,022 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 0.19 (3022 hom., cov: 32)
• Consequence: SHISA6 NM_207386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445
• Publications: 1 publications found

Genes affected

SHISA6 (HGNC:34491): (shisa family member 6) Predicted to enable ionotropic glutamate receptor binding activity. Predicted to be involved in several processes, including excitatory chemical synaptic transmission; regulation of short-term neuronal synaptic plasticity; and regulation of signal transduction. Predicted to be located in asymmetric, glutamatergic, excitatory 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 = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207386.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHISA6	NM_207386.4	MANE Select	c.800-42309G>A		intron	N/A	NP_997269.2	Q6ZSJ9-3
	SHISA6	NM_001173462.2		c.800-42309G>A		intron	N/A	NP_001166933.1	Q6ZSJ9-2
	SHISA6	NM_001173461.2		c.799+73579G>A		intron	N/A	NP_001166932.1	Q6ZSJ9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHISA6	ENST00000441885.8	TSL:5 MANE Select	c.800-42309G>A		intron	N/A	ENSP00000390084.3	Q6ZSJ9-3
	SHISA6	ENST00000432116.7	TSL:1	c.800-42309G>A		intron	N/A	ENSP00000388659.3	Q6ZSJ9-2
	SHISA6	ENST00000409168.7	TSL:1	c.799+73579G>A		intron	N/A	ENSP00000387157.3	Q6ZSJ9-1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29209 AN: 151952 Hom.: 3017 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.0748

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.192 AC: 29234 AN: 152070 Hom.: 3022 Cov.: 32 AF XY: 0.189 AC XY: 14020 AN XY: 74334

African (AFR) AF: 0.191 AC: 7919 AN: 41454

American (AMR) AF: 0.166 AC: 2539 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1060 AN: 3468

East Asian (EAS) AF: 0.0746 AC: 386 AN: 5176

South Asian (SAS) AF: 0.121 AC: 585 AN: 4820

European-Finnish (FIN) AF: 0.157 AC: 1659 AN: 10574

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14415 AN: 67980

Other (OTH) AF: 0.215 AC: 453 AN: 2106

Alfa AF: 0.205 Hom.: 1824

Bravo AF: 0.193

Asia WGS AF: 0.110 AC: 382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.39
PhyloP100		-0.45
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: rs12602611; hg19: chr17-11240422;