rs205023

Variant names:

• chr17-11413084-A-G
• rs205023
• NM_207386.4:c.895+33575A>G

Variant summary

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

The NM_207386.4(SHISA6):​c.895+33575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 152,100 control chromosomes in the GnomAD database, including 618 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 0.080 (618 hom., cov: 32)
• Consequence: SHISA6 NM_207386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.138 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.895+33575A>G		intron	N/A	NP_997269.2	Q6ZSJ9-3
	SHISA6	NM_001173462.2		c.895+33575A>G		intron	N/A	NP_001166933.1	Q6ZSJ9-2
	SHISA6	NM_001173461.2		c.800-142656A>G		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.895+33575A>G		intron	N/A	ENSP00000390084.3	Q6ZSJ9-3
	SHISA6	ENST00000432116.7	TSL:1	c.895+33575A>G		intron	N/A	ENSP00000388659.3	Q6ZSJ9-2
	SHISA6	ENST00000409168.7	TSL:1	c.800-142656A>G		intron	N/A	ENSP00000387157.3	Q6ZSJ9-1

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 12097 AN: 151980 Hom.: 620 Cov.: 32

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0925

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0795 AC: 12097 AN: 152100 Hom.: 618 Cov.: 32 AF XY: 0.0842 AC XY: 6259 AN XY: 74338

African (AFR) AF: 0.0190 AC: 788 AN: 41512

American (AMR) AF: 0.118 AC: 1798 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0937 AC: 325 AN: 3470

East Asian (EAS) AF: 0.120 AC: 617 AN: 5134

South Asian (SAS) AF: 0.147 AC: 704 AN: 4804

European-Finnish (FIN) AF: 0.117 AC: 1241 AN: 10590

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0925 AC: 6287 AN: 67996

Other (OTH) AF: 0.0710 AC: 150 AN: 2112

Alfa AF: 0.0886 Hom.: 1086

Bravo AF: 0.0750

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.63
DANN	Benign	0.62
PhyloP100		-0.12
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: rs205023; hg19: chr17-11316401;