16-12902182-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001145204.3(SHISA9):c.118C>G(p.Leu40Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: SHISA9 NM_001145204.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.06

Genes affected

SHISA9 (HGNC:37231): (shisa family member 9) Predicted to enable PDZ domain binding activity. Predicted to be involved in regulation of AMPA receptor activity and regulation of short-term neuronal synaptic plasticity. Predicted to be located in 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 density membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.085163206).
• BP6: Variant 16-12902182-C-G is Benign according to our data. Variant chr16-12902182-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2534554.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHISA9	NM_001145204.3	c.118C>G	p.Leu40Val	missense_variant	1/5	ENST00000558583.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHISA9	ENST00000558583.3	c.118C>G	p.Leu40Val	missense_variant	1/5	5	NM_001145204.3	P1
SHISA9	ENST00000423335.2	c.118C>G	p.Leu40Val	missense_variant	1/2	1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	18
Dann	Benign	0.37
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.59	T;T;T
M_CAP	Uncertain	0.29	D
MetaRNN	Benign	0.085	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.98	N;N;N;N
PrimateAI	Pathogenic	0.93	D
Polyphen		0.0	.;B;B
Vest4		0.074, 0.11
MutPred		0.31		Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);
MVP		0.030
ClinPred		0.019	T
GERP RS		0.95
Varity_R		0.045
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-12996039;