Variant 1-159943055-A-G 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.155T>C(p.Leu52Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,612,994 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

IGSF9
NM_001135050.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

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:

Genome browser will be placed here

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=0.20737988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF9	NM_001135050.2 linkuse as main transcript	c.155T>C	p.Leu52Pro	missense_variant	3/21	ENST00000368094.6	NP_001128522.1	Q9P2J2-1
IGSF9	NM_020789.4 linkuse as main transcript	c.155T>C	p.Leu52Pro	missense_variant	3/21		NP_065840.2	Q9P2J2-2
LOC124904438	XR_007066684.1 linkuse as main transcript	n.78+1609A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IGSF9	ENST00000368094.6 linkuse as main transcript	c.155T>C	p.Leu52Pro	missense_variant	3/21	1	NM_001135050.2	ENSP00000357073.1	Q9P2J2-1
IGSF9	ENST00000361509.7 linkuse as main transcript	c.155T>C	p.Leu52Pro	missense_variant	3/21	1		ENSP00000355049.3	Q9P2J2-2
IGSF9	ENST00000476102.1 linkuse as main transcript	n.350T>C		non_coding_transcript_exon_variant	3/20	5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151998

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

245112

Hom.:

AF XY:

0.00000751

AC XY:

AN XY:

133154

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:

0.0000273

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460996

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726800

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151998

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

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

Jul 20, 2022

The c.155T>C (p.L52P) alteration is located in exon 3 (coding exon 2) of the IGSF9 gene. This alteration results from a T to C substitution at nucleotide position 155, causing the leucine (L) at amino acid position 52 to be replaced by a proline (P). 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

Pathogenic

0.63

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

.;T;T

Eigen

Benign

-0.080

Eigen_PC

Benign

0.030

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.46

N;N;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

2.0

N;N;.

REVEL

Benign

0.20

Sift

Benign

0.072

T;T;.

Sift4G

Benign

0.094

T;T;T

Polyphen

1.0

.;D;.

Vest4

0.52

MutPred

0.53

Gain of disorder (P = 0.0284);Gain of disorder (P = 0.0284);Gain of disorder (P = 0.0284);

MVP

0.11

MPC

1.2

ClinPred

0.71

GERP RS

4.8

Varity_R

0.17

gMVP

0.74

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