chr17-11445488-C-T

Variant names:

• chr17-11445488-C-T
• rs11656526
• NM_207386.4:c.895+65979C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207386.4(SHISA6):​c.895+65979C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0346 in 152,286 control chromosomes in the GnomAD database, including 128 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 0.035 (128 hom., cov: 33)
• Consequence: SHISA6 NM_207386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISA6	NM_207386.4	c.895+65979C>T		intron_variant	Intron 3 of 5	ENST00000441885.8	NP_997269.2
SHISA6	NM_001173462.2	c.895+65979C>T		intron_variant	Intron 3 of 4		NP_001166933.1
SHISA6	NM_001173461.2	c.800-110252C>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+65979C>T		intron_variant	Intron 3 of 5	5	NM_207386.4	ENSP00000390084.3
SHISA6	ENST00000432116.7	c.895+65979C>T		intron_variant	Intron 3 of 4	1		ENSP00000388659.3
SHISA6	ENST00000409168.7	c.800-110252C>T		intron_variant	Intron 2 of 3	1		ENSP00000387157.3

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5268 AN: 152168 Hom.: 128 Cov.: 33

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0290

Gnomad ASJ AF: 0.0518

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0536

Gnomad OTH AF: 0.0325

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

GnomAD4 genome AF: 0.0346 AC: 5267 AN: 152286 Hom.: 128 Cov.: 33 AF XY: 0.0323 AC XY: 2405 AN XY: 74470

African (AFR) AF: 0.0105 AC: 436 AN: 41544

American (AMR) AF: 0.0290 AC: 443 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0518 AC: 180 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0377 AC: 182 AN: 4824

European-Finnish (FIN) AF: 0.0207 AC: 220 AN: 10612

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0536 AC: 3643 AN: 68026

Other (OTH) AF: 0.0322 AC: 68 AN: 2114

Alfa AF: 0.0502 Hom.: 267

Bravo AF: 0.0344

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.15
DANN	Benign	0.72
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

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: rs11656526; hg19: chr17-11348805;