19-55433560-C-T

Variant names:

• chr19-55433560-C-T
• rs1474078592
• NM_001145176.2:c.1213G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145176.2(SHISA7):​c.1213G>A​(p.Ala405Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000669 in 1,494,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A405V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000067 (0 hom.)
• Consequence: SHISA7 NM_001145176.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42
• Publications: 1 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: 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=0.09419021).

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.1213G>A	p.Ala405Thr	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.1213G>A	p.Ala405Thr	missense	Exon 4 of 4	ENSP00000365503.3	A6NL88
	SHISA7	ENST00000416792.2	TSL:5	c.1279G>A	p.Ala427Thr	missense	Exon 5 of 5	ENSP00000401307.2	H7C1N4

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151970 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000670 AC: 9 AN: 1342954 Hom.: 0 Cov.: 31 AF XY: 0.00000604 AC XY: 4 AN XY: 662404

African (AFR) AF: 0.00 AC: 0 AN: 27062

American (AMR) AF: 0.00 AC: 0 AN: 30350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23666

East Asian (EAS) AF: 0.00 AC: 0 AN: 29766

South Asian (SAS) AF: 0.00 AC: 0 AN: 75222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5520

European-Non Finnish (NFE) AF: 0.00000849 AC: 9 AN: 1060660

Other (OTH) AF: 0.00 AC: 0 AN: 55914

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151970 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74244

African (AFR) AF: 0.00 AC: 0 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67952

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.43	D
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.4
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.035
Sift	Benign	0.11	T
Sift4G	Benign	0.57	T
Polyphen		0.11	B
Vest4		0.20
MutPred		0.25		Loss of stability (P = 0.0349)
MVP		0.030
ClinPred		0.17	T
GERP RS		2.6
Varity_R		0.094
gMVP		0.15
Mutation Taster		=94/6	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: rs1474078592; hg19: chr19-55944927;