chr17-11482573-C-T

Position:

• chr17-11482573-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.896-69323C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,164 control chromosomes in the GnomAD database, including 2,664 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 0.18 (2664 hom., cov: 33)
• Consequence: SHISA6 NM_207386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHISA6	NM_207386.4	c.896-69323C>T		intron_variant		ENST00000441885.8	NP_997269.2
SHISA6	NM_001173461.2	c.800-73167C>T		intron_variant			NP_001166932.1
SHISA6	NM_001173462.2	c.896-73167C>T		intron_variant			NP_001166933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHISA6	ENST00000441885.8	c.896-69323C>T		intron_variant		5	NM_207386.4	ENSP00000390084
SHISA6	ENST00000409168.7	c.800-73167C>T		intron_variant		1		ENSP00000387157	P1
SHISA6	ENST00000432116.7	c.896-73167C>T		intron_variant		1		ENSP00000388659

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27576 AN: 152048 Hom.: 2663 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.181 AC: 27598 AN: 152164 Hom.: 2664 Cov.: 33 AF XY: 0.182 AC XY: 13537 AN XY: 74404

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.216

Alfa AF: 0.187 Hom.: 3681

Bravo AF: 0.189

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.2
DANN	Benign	0.88

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: rs4792143; hg19: chr17-11385890;