17-11415001-G-T

Variant names:

• chr17-11415001-G-T
• rs205017
• NM_207386.4:c.895+35492G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207386.4(SHISA6):​c.895+35492G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,480 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 29)
• Consequence: SHISA6 NM_207386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISA6	NM_207386.4	c.895+35492G>T		intron_variant	Intron 3 of 5	ENST00000441885.8	NP_997269.2
SHISA6	NM_001173462.2	c.895+35492G>T		intron_variant	Intron 3 of 4		NP_001166933.1
SHISA6	NM_001173461.2	c.800-140739G>T		intron_variant	Intron 2 of 3		NP_001166932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHISA6	ENST00000441885.8	c.895+35492G>T		intron_variant	Intron 3 of 5	5	NM_207386.4	ENSP00000390084.3
SHISA6	ENST00000432116.7	c.895+35492G>T		intron_variant	Intron 3 of 4	1		ENSP00000388659.3
SHISA6	ENST00000409168.7	c.800-140739G>T		intron_variant	Intron 2 of 3	1		ENSP00000387157.3

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151480 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151480 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 73902

African (AFR) AF: 0.0000243 AC: 1 AN: 41228

American (AMR) AF: 0.00 AC: 0 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67882

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 1690

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.35
DANN	Benign	0.80
PhyloP100		-2.0

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: rs205017; hg19: chr17-11318318;