17-11503942-T-A

Variant names:

• chr17-11503942-T-A
• rs2908972
• NM_207386.4:c.896-47954T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_207386.4(SHISA6):​c.896-47954T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,150 control chromosomes in the GnomAD database, including 11,533 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 0.39 (11533 hom., cov: 33)
• Consequence: SHISA6 NM_207386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.397
• Publications: 15 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.529 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.896-47954T>A		intron	N/A	NP_997269.2	Q6ZSJ9-3
	SHISA6	NM_001173462.2		c.896-51798T>A		intron	N/A	NP_001166933.1	Q6ZSJ9-2
	SHISA6	NM_001173461.2		c.800-51798T>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.896-47954T>A		intron	N/A	ENSP00000390084.3	Q6ZSJ9-3
	SHISA6	ENST00000432116.7	TSL:1	c.896-51798T>A		intron	N/A	ENSP00000388659.3	Q6ZSJ9-2
	SHISA6	ENST00000409168.7	TSL:1	c.800-51798T>A		intron	N/A	ENSP00000387157.3	Q6ZSJ9-1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59133 AN: 152032 Hom.: 11532 Cov.: 33

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.389 AC: 59155 AN: 152150 Hom.: 11533 Cov.: 33 AF XY: 0.392 AC XY: 29123 AN XY: 74376

African (AFR) AF: 0.350 AC: 14524 AN: 41506

American (AMR) AF: 0.373 AC: 5698 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1481 AN: 3468

East Asian (EAS) AF: 0.546 AC: 2823 AN: 5168

South Asian (SAS) AF: 0.461 AC: 2223 AN: 4826

European-Finnish (FIN) AF: 0.383 AC: 4056 AN: 10602

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26889 AN: 67990

Other (OTH) AF: 0.426 AC: 898 AN: 2108

Alfa AF: 0.385 Hom.: 1386

Bravo AF: 0.390

Asia WGS AF: 0.447 AC: 1556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.76
PhyloP100		0.40
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: rs2908972; hg19: chr17-11407259;