Variant 16-13203423-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145204.3(SHISA9):c.721A>G(p.Thr241Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,546,898 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

SHISA9
NM_001145204.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10

Variant links:

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]

SHISA9 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.041790873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHISA9	NM_001145204.3 linkuse as main transcript	c.721A>G	p.Thr241Ala	missense_variant	3/5	ENST00000558583.3	NP_001138676.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHISA9	ENST00000558583.3 linkuse as main transcript	c.721A>G	p.Thr241Ala	missense_variant	3/5	5	NM_001145204.3	ENSP00000454014	P1	B4DS77-1
	ENST00000571939.1 linkuse as main transcript	n.171T>C		non_coding_transcript_exon_variant	2/3	3
SHISA9	ENST00000566106.1 linkuse as main transcript	n.165A>G		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes

AF:

0.000501

AC:

AN:

151774

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000787

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000810

Gnomad OTH

AF:

0.000962

GnomAD3 exomes

AF:

0.000460

AC:

AN:

154264

Hom.:

AF XY:

0.000406

AC XY:

AN XY:

81258

show subpopulations

Gnomad AFR exome

AF:

0.000243

Gnomad AMR exome

AF:

0.000547

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000883

Gnomad OTH exome

AF:

0.000688

GnomAD4 exome

AF:

0.00106

AC:

1480

AN:

1395124

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

696

AN XY:

688064

show subpopulations

Gnomad4 AFR exome

AF:

0.000191

Gnomad4 AMR exome

AF:

0.000605

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00132

Gnomad4 OTH exome

AF:

0.000621

GnomAD4 genome

AF:

0.000501

AC:

AN:

151774

Hom.:

Cov.:

AF XY:

0.000661

AC XY:

AN XY:

74108

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000787

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000190

Gnomad4 NFE

AF:

0.000810

Gnomad4 OTH

AF:

0.000962

Alfa

AF:

0.000654

Hom.:

Bravo

AF:

0.000544

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.000144

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.721A>G (p.T241A) alteration is located in exon 3 (coding exon 3) of the SHISA9 gene. This alteration results from a A to G substitution at nucleotide position 721, causing the threonine (T) at amino acid position 241 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

Eigen

Benign

-0.075

Eigen_PC

Benign

0.062

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.58

M_CAP

Benign

0.0080

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

MutationTaster

Benign

0.63

N;N

PrimateAI

Uncertain

0.49

Sift4G

Benign

0.37

Polyphen

0.28

Vest4

0.20

MVP

0.11

ClinPred

0.031

GERP RS

4.7

Varity_R

0.11

gMVP

0.42

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over