17-11439291-G-A

Variant names:

• chr17-11439291-G-A
• rs1877644
• NM_207386.4:c.895+59782G>A

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+59782G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,094 control chromosomes in the GnomAD database, including 6,413 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 0.25 (6413 hom., cov: 32)
• Consequence: SHISA6 NM_207386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507
• Publications: 4 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHISA6	NM_207386.4	MANE Select	c.895+59782G>A		intron	N/A	NP_997269.2
	SHISA6	NM_001173462.2		c.895+59782G>A		intron	N/A	NP_001166933.1
	SHISA6	NM_001173461.2		c.800-116449G>A		intron	N/A	NP_001166932.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHISA6	ENST00000441885.8	TSL:5 MANE Select	c.895+59782G>A		intron	N/A	ENSP00000390084.3
	SHISA6	ENST00000432116.7	TSL:1	c.895+59782G>A		intron	N/A	ENSP00000388659.3
	SHISA6	ENST00000409168.7	TSL:1	c.800-116449G>A		intron	N/A	ENSP00000387157.3

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37751 AN: 151974 Hom.: 6386 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.249 AC: 37822 AN: 152094 Hom.: 6413 Cov.: 32 AF XY: 0.247 AC XY: 18343 AN XY: 74350

African (AFR) AF: 0.479 AC: 19848 AN: 41430

American (AMR) AF: 0.222 AC: 3396 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 446 AN: 3470

East Asian (EAS) AF: 0.0620 AC: 321 AN: 5174

South Asian (SAS) AF: 0.314 AC: 1513 AN: 4820

European-Finnish (FIN) AF: 0.137 AC: 1450 AN: 10600

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10101 AN: 68004

Other (OTH) AF: 0.255 AC: 539 AN: 2112

Alfa AF: 0.195 Hom.: 7494

Bravo AF: 0.264

Asia WGS AF: 0.222 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.55
PhyloP100		-0.51
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: rs1877644; hg19: chr17-11342608;