Genetic Variant NM_001135050.2:c.2774A>G (chr1-159928614-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001135050.2(IGSF9):c.2774A>G(p.Gln925Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,344,236 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: not found (cov: 33)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

IGSF9
NM_001135050.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.86

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24325976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF9	NM_001135050.2 link	c.2774A>G	p.Gln925Arg	missense_variant	Exon 19 of 21	ENST00000368094.6	NP_001128522.1	Q9P2J2-1
IGSF9	NM_020789.4 link	c.2726A>G	p.Gln909Arg	missense_variant	Exon 19 of 21		NP_065840.2	Q9P2J2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF9	ENST00000368094.6 link	c.2774A>G	p.Gln925Arg	missense_variant	Exon 19 of 21	1	NM_001135050.2	ENSP00000357073.1		Q9P2J2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000372

AC:

AN:

1344236

Hom.:

Cov.:

AF XY:

0.00000152

AC XY:

AN XY:

656052

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30370

American (AMR)

AF:

0.00

AC:

AN:

26528

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19946

East Asian (EAS)

AF:

0.00

AC:

AN:

37456

South Asian (SAS)

AF:

0.00

AC:

AN:

67928

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47912

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5324

European-Non Finnish (NFE)

AF:

0.00000475

AC:

AN:

1053274

Other (OTH)

AF:

0.00

AC:

AN:

55498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2774A>G (p.Q925R) alteration is located in exon 19 (coding exon 18) of the IGSF9 gene. This alteration results from a A to G substitution at nucleotide position 2774, causing the glutamine (Q) at amino acid position 925 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

Benign

0.20

BayesDel_addAF

Uncertain

0.067

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

.;T;T

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.078

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.2

.;M;.

PhyloP100

4.9

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.59

N;N;.

REVEL

Benign

0.22

Sift

Pathogenic

0.0

D;D;.

Sift4G

Benign

0.40

T;T;T

Polyphen

0.99

.;D;.

Vest4

0.68

MutPred

0.27

.;Gain of phosphorylation at S928 (P = 0.0602);.;

MVP

0.31

MPC

0.91

ClinPred

0.94

GERP RS

3.5

Varity_R

0.25

gMVP

0.48

Mutation Taster

=57/43

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_001135050.2:c.2774A>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over