Variant 17-11241612-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207386.4(SHISA6):c.190G>T(p.Ala64Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000862 in 1,160,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.6e-7 ( 0 hom. )

Consequence

SHISA6
NM_207386.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0770

Variant links:

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]

SHISA6 links:

ENSG00000285541 (HGNC:):

ENSG00000285541 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05999434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SHISA6	NM_207386.4 link	c.190G>T	p.Ala64Ser	missense_variant	1/6	ENST00000441885.8	NP_997269.2
SHISA6	NM_001173462.2 link	c.190G>T	p.Ala64Ser	missense_variant	1/5		NP_001166933.1
SHISA6	NM_001173461.2 link	c.190G>T	p.Ala64Ser	missense_variant	1/4		NP_001166932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SHISA6	ENST00000441885.8 link	c.190G>T	p.Ala64Ser	missense_variant	1/6	5	NM_207386.4	ENSP00000390084.3	Q6ZSJ9-3
SHISA6	ENST00000432116.7 link	c.190G>T	p.Ala64Ser	missense_variant	1/5	1		ENSP00000388659.3	Q6ZSJ9-2
SHISA6	ENST00000409168.7 link	c.190G>T	p.Ala64Ser	missense_variant	1/4	1		ENSP00000387157.3	Q6ZSJ9-1
ENSG00000285541	ENST00000648331.1 link	n.98+353C>A		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.62e-7

AC:

AN:

1160680

Hom.:

Cov.:

AF XY:

0.00000178

AC XY:

AN XY:

560670

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2021

The c.190G>T (p.A64S) alteration is located in exon 1 (coding exon 1) of the SHISA6 gene. This alteration results from a G to T substitution at nucleotide position 190, causing the alanine (A) at amino acid position 64 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0076

.;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.47

T;T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.060

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.60

N;N;N

REVEL

Benign

0.031

Sift

Benign

0.30

T;T;T

Sift4G

Benign

0.76

T;T;T

Polyphen

0.11

B;.;B

Vest4

0.079

MutPred

0.17

Gain of glycosylation at A64 (P = 0.0254);Gain of glycosylation at A64 (P = 0.0254);Gain of glycosylation at A64 (P = 0.0254);

MVP

0.014

ClinPred

0.049

GERP RS

-2.9

Varity_R

0.041

gMVP

0.23

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over