chr19-55433742-C-T

Variant names:

• chr19-55433742-C-T
• rs976204726
• NM_001145176.2:c.1031G>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.1031G>A​(p.Arg344His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000765 in 1,306,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: SHISA7 NM_001145176.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.67
• 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: 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=0.19731545).

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.1031G>A	p.Arg344His	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.1031G>A	p.Arg344His	missense	Exon 4 of 4	ENSP00000365503.3	A6NL88
	SHISA7	ENST00000416792.2	TSL:5	c.1097G>A	p.Arg366His	missense	Exon 5 of 5	ENSP00000401307.2	H7C1N4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.65e-7 AC: 1 AN: 1306708 Hom.: 0 Cov.: 31 AF XY: 0.00000155 AC XY: 1 AN XY: 643228

African (AFR) AF: 0.00 AC: 0 AN: 25822

American (AMR) AF: 0.00 AC: 0 AN: 21276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21916

East Asian (EAS) AF: 0.00 AC: 0 AN: 28524

South Asian (SAS) AF: 0.00 AC: 0 AN: 69896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4998

European-Non Finnish (NFE) AF: 9.55e-7 AC: 1 AN: 1047424

Other (OTH) AF: 0.00 AC: 0 AN: 54370

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.26
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.042
Eigen_PC	Benign	-0.0041
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.7
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.020	D
Polyphen		0.89	P
Vest4		0.14
MutPred		0.51		Loss of methylation at R344 (P = 0.0137)
MVP		0.040
ClinPred		0.97	D
GERP RS		2.4
Varity_R		0.42
gMVP		0.36
Mutation Taster		=69/31	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: rs976204726; hg19: chr19-55945109;