Genetic Variant NM_001135050.2:c.2836G>T (chr1-159928552-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001135050.2(IGSF9):c.2836G>T(p.Glu946*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IGSF9
NM_001135050.2 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.428

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF9	NM_001135050.2 link	c.2836G>T	p.Glu946*	stop_gained	Exon 19 of 21	ENST00000368094.6	NP_001128522.1	Q9P2J2-1
IGSF9	NM_020789.4 link	c.2788G>T	p.Glu930*	stop_gained	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.2836G>T	p.Glu946*	stop_gained	Exon 19 of 21	1	NM_001135050.2	ENSP00000357073.1		Q9P2J2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1393140

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

685156

African (AFR)

AF:

0.00

AC:

AN:

31768

American (AMR)

AF:

0.00

AC:

AN:

34788

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22178

East Asian (EAS)

AF:

0.00

AC:

AN:

38598

South Asian (SAS)

AF:

0.00

AC:

AN:

75916

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5460

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076768

Other (OTH)

AF:

0.00

AC:

AN:

57356

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.51

BayesDel_noAF

Pathogenic

0.49

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.75

PhyloP100

0.43

Vest4

0.20

GERP RS

3.6

Mutation Taster

=24/176

disease causing (fs/PTC)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over