Variant 1-159943077-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001135050.2(IGSF9):c.133C>T(p.Pro45Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000041 ( 0 hom. )

Consequence

IGSF9
NM_001135050.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.972

Variant links:

Genes affected

IGSF9 (HGNC:18132): (immunoglobulin superfamily member 9) Predicted to enable cell-cell adhesion mediator activity. Predicted to be involved in axon guidance; dendrite self-avoidance; and homophilic cell adhesion via plasma membrane adhesion molecules. Predicted to act upstream of or within dendrite development and regulation of synapse organization. Predicted to be located in dendrite and inhibitory synapse. Predicted to be integral component of membrane. Predicted to be active in axon and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

IGSF9 links:

IGSF9 (HGNC:):

IGSF9 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21194696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF9	NM_001135050.2 linkuse as main transcript	c.133C>T	p.Pro45Ser	missense_variant	3/21	ENST00000368094.6	NP_001128522.1	Q9P2J2-1
IGSF9	NM_020789.4 linkuse as main transcript	c.133C>T	p.Pro45Ser	missense_variant	3/21		NP_065840.2	Q9P2J2-2
LOC124904438	XR_007066684.1 linkuse as main transcript	n.78+1631G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IGSF9	ENST00000368094.6 linkuse as main transcript	c.133C>T	p.Pro45Ser	missense_variant	3/21	1	NM_001135050.2	ENSP00000357073.1	Q9P2J2-1
IGSF9	ENST00000361509.7 linkuse as main transcript	c.133C>T	p.Pro45Ser	missense_variant	3/21	1		ENSP00000355049.3	Q9P2J2-2
IGSF9	ENST00000476102.1 linkuse as main transcript	n.328C>T		non_coding_transcript_exon_variant	3/20	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

246448

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133646

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000272

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460580

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726568

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000151

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

Sep 22, 2023

The c.133C>T (p.P45S) alteration is located in exon 3 (coding exon 2) of the IGSF9 gene. This alteration results from a C to T substitution at nucleotide position 133, causing the proline (P) at amino acid position 45 to be replaced by a serine (S). 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

0.13

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.039

.;T;T

Eigen

Benign

-0.064

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.63

T;T;T

M_CAP

Benign

0.058

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.1

M;M;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.5

N;N;.

REVEL

Benign

0.17

Sift

Benign

0.41

T;T;.

Sift4G

Benign

0.39

T;T;T

Polyphen

0.47

.;P;.

Vest4

0.23

MutPred

0.41

Loss of glycosylation at P46 (P = 0.0963);Loss of glycosylation at P46 (P = 0.0963);Loss of glycosylation at P46 (P = 0.0963);

MVP

0.44

MPC

0.25

ClinPred

0.066

GERP RS

3.0

Varity_R

0.037

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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