17-11563878-C-T

Variant names:

• chr17-11563878-C-T
• rs9227
• NM_207386.4:c.*5574C>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.*5574C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.396 in 151,968 control chromosomes in the GnomAD database, including 12,271 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 0.40 (12271 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: SHISA6 NM_207386.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.61
• Publications: 7 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=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 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.*5574C>T		3_prime_UTR	Exon 6 of 6	NP_997269.2	Q6ZSJ9-3
	SHISA6	NM_001173462.2		c.*5574C>T		3_prime_UTR	Exon 5 of 5	NP_001166933.1	Q6ZSJ9-2
	SHISA6	NM_001173461.2		c.*5574C>T		3_prime_UTR	Exon 4 of 4	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.*5574C>T		3_prime_UTR	Exon 6 of 6	ENSP00000390084.3	Q6ZSJ9-3
	SHISA6	ENST00000432116.7	TSL:1	c.*5574C>T		3_prime_UTR	Exon 5 of 5	ENSP00000388659.3	Q6ZSJ9-2
	SHISA6	ENST00000409168.7	TSL:1	c.*5574C>T		3_prime_UTR	Exon 4 of 4	ENSP00000387157.3	Q6ZSJ9-1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60105 AN: 151846 Hom.: 12257 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.396

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.396 AC: 60165 AN: 151964 Hom.: 12271 Cov.: 32 AF XY: 0.390 AC XY: 28959 AN XY: 74280

African (AFR) AF: 0.487 AC: 20182 AN: 41432

American (AMR) AF: 0.304 AC: 4638 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1725 AN: 3468

East Asian (EAS) AF: 0.338 AC: 1747 AN: 5164

South Asian (SAS) AF: 0.343 AC: 1657 AN: 4824

European-Finnish (FIN) AF: 0.289 AC: 3047 AN: 10558

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25887 AN: 67940

Other (OTH) AF: 0.395 AC: 831 AN: 2104

Alfa AF: 0.386 Hom.: 6187

Bravo AF: 0.399

Asia WGS AF: 0.389 AC: 1355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.2
DANN	Benign	0.81
PhyloP100		3.6
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: rs9227; hg19: chr17-11467195; COSMIC: COSV69394213;