chr1-159928552-C-A

Variant names:

• chr1-159928552-C-A
• rs761756334
• NM_001135050.2:c.2836G>T

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.428
• Publications: 0 publications found

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]

ACMG classification

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	c.2836G>T	p.Glu946*	stop_gained	Exon 19 of 21	ENST00000368094.6	NP_001128522.1
IGSF9	NM_020789.4	c.2788G>T	p.Glu930*	stop_gained	Exon 19 of 21		NP_065840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF9	ENST00000368094.6	c.2836G>T	p.Glu946*	stop_gained	Exon 19 of 21	1	NM_001135050.2	ENSP00000357073.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1393140 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 685156

African (AFR) AF: 0.00 AC: 0 AN: 31768

American (AMR) AF: 0.00 AC: 0 AN: 34788

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22178

East Asian (EAS) AF: 0.00 AC: 0 AN: 38598

South Asian (SAS) AF: 0.00 AC: 0 AN: 75916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5460

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076768

Other (OTH) AF: 0.00 AC: 0 AN: 57356

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.49
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.75	D
PhyloP100		0.43
Vest4		0.20
GERP RS		3.6
Mutation Taster		=24/176	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs761756334; hg19: chr1-159898342;