chr17-11563878-C-T

Variant names:

• chr17-11563878-C-T
• rs9227
• NM_207386.4:c.*5574C>T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISA6	NM_207386.4	c.*5574C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000441885.8	NP_997269.2
SHISA6	NM_001173462.2	c.*5574C>T		3_prime_UTR_variant	Exon 5 of 5		NP_001166933.1
SHISA6	NM_001173461.2	c.*5574C>T		3_prime_UTR_variant	Exon 4 of 4		NP_001166932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHISA6	ENST00000441885.8	c.*5574C>T		3_prime_UTR_variant	Exon 6 of 6	5	NM_207386.4	ENSP00000390084.3
SHISA6	ENST00000432116.7	c.*5574C>T		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000388659.3
SHISA6	ENST00000409168.7	c.*5574C>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000387157.3

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

Gnomad4 NFE exome AF: 0.500

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

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.395

Alfa AF: 0.385 Hom.: 5526

Bravo AF: 0.399

Asia WGS AF: 0.389 AC: 1355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.2
DANN	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs9227; hg19: chr17-11467195; COSMIC: COSV69394213;