Variant 1-159943426-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000368094.6(IGSF9):c.29T>G(p.Leu10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000835 in 1,436,678 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

IGSF9
ENST00000368094.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.05

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:

LOC124904438 (HGNC:):

LOC124904438 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IGSF9	NM_001135050.2 linkuse as main transcript	c.29T>G	p.Leu10Arg	missense_variant	2/21	ENST00000368094.6	NP_001128522.1
LOC124904438	XR_007066684.1 linkuse as main transcript	n.78+1980A>C		intron_variant, non_coding_transcript_variant
IGSF9	NM_020789.4 linkuse as main transcript	c.29T>G	p.Leu10Arg	missense_variant	2/21		NP_065840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF9	ENST00000368094.6 linkuse as main transcript	c.29T>G	p.Leu10Arg	missense_variant	2/21	1	NM_001135050.2	ENSP00000357073	P1	Q9P2J2-1
IGSF9	ENST00000361509.7 linkuse as main transcript	c.29T>G	p.Leu10Arg	missense_variant	2/21	1		ENSP00000355049		Q9P2J2-2
IGSF9	ENST00000476102.1 linkuse as main transcript	n.224T>G		non_coding_transcript_exon_variant	2/20	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000835

AC:

AN:

1436678

Hom.:

Cov.:

AF XY:

0.00000983

AC XY:

AN XY:

712328

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000100

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

Cov.:

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

Mar 21, 2022

The c.29T>G (p.L10R) alteration is located in exon 2 (coding exon 1) of the IGSF9 gene. This alteration results from a T to G substitution at nucleotide position 29, causing the leucine (L) at amino acid position 10 to be replaced by an arginine (R). 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

0.59

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

.;T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.071

MetaRNN

Uncertain

0.74

D;D;D

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.4

L;L;.

MutationTaster

Benign

0.83

D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.9

N;N;.

REVEL

Uncertain

0.43

Sift

Uncertain

0.0030

D;D;.

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.90

MutPred

0.75

Gain of MoRF binding (P = 0.0021);Gain of MoRF binding (P = 0.0021);Gain of MoRF binding (P = 0.0021);

MVP

0.19

MPC

0.46

ClinPred

0.78

GERP RS

4.8

Varity_R

0.44

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over