Genetic Variant SHISA7:p.Gly373Ser (chr19-55433656-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145176.2(SHISA7):c.1117G>A(p.Gly373Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000747 in 1,337,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 7.5e-7 ( 0 hom. )

Consequence

SHISA7
NM_001145176.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.829

Publications

0 publications found

Variant links:

Genes affected

SHISA7 (HGNC:35409): (shisa family member 7) Predicted to enable GABA receptor binding activity and ionotropic glutamate receptor binding activity. Predicted to be involved in several processes, including gamma-aminobutyric acid receptor clustering; regulation of signaling receptor activity; and regulation of synaptic plasticity. 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 specialization membrane. [provided by Alliance of Genome Resources, Apr 2022]

SHISA7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056245).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145176.2. 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
	SHISA7	NM_001145176.2	MANE Select	c.1117G>A	p.Gly373Ser	missense	Exon 4 of 4	NP_001138648.1	A6NL88

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHISA7	ENST00000376325.10	TSL:2 MANE Select	c.1117G>A	p.Gly373Ser	missense	Exon 4 of 4	ENSP00000365503.3	A6NL88
	SHISA7	ENST00000416792.2	TSL:5	c.1183G>A	p.Gly395Ser	missense	Exon 5 of 5	ENSP00000401307.2	H7C1N4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.47e-7

AC:

AN:

1337860

Hom.:

Cov.:

AF XY:

0.00000152

AC XY:

AN XY:

659614

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26980

American (AMR)

AF:

0.00

AC:

AN:

29038

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23578

East Asian (EAS)

AF:

0.00

AC:

AN:

29550

South Asian (SAS)

AF:

0.0000134

AC:

AN:

74560

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5436

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1059506

Other (OTH)

AF:

0.00

AC:

AN:

55708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0099

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.58

M_CAP

Pathogenic

0.55

MetaRNN

Benign

0.056

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.14

PhyloP100

-0.83

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.16

REVEL

Benign

0.035

Sift

Benign

0.89

Sift4G

Benign

0.71

Polyphen

0.028

Vest4

0.044

MutPred

0.17

Gain of glycosylation at G373 (P = 0.0054)

MVP

0.030

ClinPred

0.048

GERP RS

1.3

Varity_R

0.072

gMVP

0.19

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over