19-55433656-C-T

Variant names:

• chr19-55433656-C-T
• rs1191366612
• NM_001145176.2:c.1117G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.829
• Publications: 0 publications found

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]

ACMG classification

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.: 32

GnomAD4 exome AF: 7.47e-7 AC: 1 AN: 1337860 Hom.: 0 Cov.: 31 AF XY: 0.00000152 AC XY: 1 AN XY: 659614

African (AFR) AF: 0.00 AC: 0 AN: 26980

American (AMR) AF: 0.00 AC: 0 AN: 29038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23578

East Asian (EAS) AF: 0.00 AC: 0 AN: 29550

South Asian (SAS) AF: 0.0000134 AC: 1 AN: 74560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5436

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1059506

Other (OTH) AF: 0.00 AC: 0 AN: 55708

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.0099	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.58	T
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.14	N
PhyloP100		-0.83
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.035
Sift	Benign	0.89	T
Sift4G	Benign	0.71	T
Polyphen		0.028	B
Vest4		0.044
MutPred		0.17		Gain of glycosylation at G373 (P = 0.0054)
MVP		0.030
ClinPred		0.048	T
GERP RS		1.3
Varity_R		0.072
gMVP		0.19
Mutation Taster		=92/8	polymorphism

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: rs1191366612; hg19: chr19-55945023;