Genetic Variant NM_001145176.2:c.1021G>C (chr19-55433752-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145176.2(SHISA7):c.1021G>C(p.Glu341Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000323 in 1,302,156 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: 0.000032 ( 0 hom. )

Consequence

SHISA7
NM_001145176.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.820

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11556843).

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.1021G>C	p.Glu341Gln	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.1021G>C	p.Glu341Gln	missense	Exon 4 of 4	ENSP00000365503.3	A6NL88
	SHISA7	ENST00000416792.2	TSL:5	c.1087G>C	p.Glu363Gln	missense	Exon 5 of 5	ENSP00000401307.2	H7C1N4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000390

AC:

AN:

51236

AF XY:

0.0000655

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000323

AC:

AN:

1302156

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

640698

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25686

American (AMR)

AF:

0.00

AC:

AN:

20278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21524

East Asian (EAS)

AF:

0.00

AC:

AN:

28502

South Asian (SAS)

AF:

0.00

AC:

AN:

69006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4960

European-Non Finnish (NFE)

AF:

0.0000383

AC:

AN:

1045708

Other (OTH)

AF:

0.0000369

AC:

AN:

54158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

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

0.20

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.48

M_CAP

Benign

0.0090

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.63

PhyloP100

-0.82

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.65

REVEL

Benign

0.061

Sift

Benign

0.22

Sift4G

Benign

0.50

Polyphen

0.99

Vest4

0.042

MutPred

0.21

Gain of MoRF binding (P = 0.0278)

MVP

0.040

ClinPred

0.20

GERP RS

2.4

Varity_R

0.15

gMVP

0.33

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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