rs205017

Positions:

• chr17-11415001-G-A
• chr17-11415001-G-C
• chr17-11415001-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207386.4(SHISA6):​c.895+35492G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,476 control chromosomes in the GnomAD database, including 33,061 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 0.66 (33061 hom., cov: 29)
• Consequence: SHISA6 NM_207386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHISA6	NM_207386.4	c.895+35492G>A		intron_variant		ENST00000441885.8
SHISA6	NM_001173461.2	c.800-140739G>A		intron_variant
SHISA6	NM_001173462.2	c.895+35492G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHISA6	ENST00000441885.8	c.895+35492G>A		intron_variant		5	NM_207386.4
SHISA6	ENST00000409168.7	c.800-140739G>A		intron_variant		1		P1
SHISA6	ENST00000432116.7	c.895+35492G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 99702 AN: 151368 Hom.: 33059 Cov.: 29

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.658 AC: 99733 AN: 151476 Hom.: 33061 Cov.: 29 AF XY: 0.656 AC XY: 48537 AN XY: 73962

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.701

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.694

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.653

Alfa AF: 0.580 Hom.: 1690

Bravo AF: 0.663

Asia WGS AF: 0.517 AC: 1797 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	0.74
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs205017; hg19: chr17-11318318;