rs8076431

Positions:

• chr17-11346902-C-A
• chr17-11346902-C-T

Variant summary

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

The NM_207386.4(SHISA6):​c.800-32512C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,074 control chromosomes in the GnomAD database, including 3,018 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 (3018 hom., cov: 33)
• Consequence: SHISA6 NM_207386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHISA6	NM_207386.4	c.800-32512C>A		intron_variant		ENST00000441885.8
SHISA6	NM_001173461.2	c.799+83376C>A		intron_variant
SHISA6	NM_001173462.2	c.800-32512C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHISA6	ENST00000441885.8	c.800-32512C>A		intron_variant		5	NM_207386.4
SHISA6	ENST00000409168.7	c.799+83376C>A		intron_variant		1		P1
SHISA6	ENST00000432116.7	c.800-32512C>A		intron_variant		1
SHISA6	ENST00000343478.7	c.282-32512C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29009 AN: 151954 Hom.: 3009 Cov.: 33

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.191 AC: 29061 AN: 152074 Hom.: 3018 Cov.: 33 AF XY: 0.195 AC XY: 14521 AN XY: 74326

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.185

Alfa AF: 0.128 Hom.: 511

Bravo AF: 0.195

Asia WGS AF: 0.230 AC: 801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.72

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: rs8076431; hg19: chr17-11250219;