NM_001135050.2:c.2878C>G

Variant names:

• chr1-159928510-G-C
• rs772497737
• NM_001135050.2:c.2878C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001135050.2(IGSF9):​c.2878C>G​(p.Arg960Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R960C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IGSF9 NM_001135050.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049470782).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF9	NM_001135050.2	c.2878C>G	p.Arg960Gly	missense_variant	Exon 19 of 21	ENST00000368094.6	NP_001128522.1
IGSF9	NM_020789.4	c.2830C>G	p.Arg944Gly	missense_variant	Exon 19 of 21		NP_065840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF9	ENST00000368094.6	c.2878C>G	p.Arg960Gly	missense_variant	Exon 19 of 21	1	NM_001135050.2	ENSP00000357073.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.031	.;T;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.049	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;.
PhyloP100		1.8
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.18	N;N;.
REVEL	Benign	0.040
Sift	Benign	0.063	T;T;.
Sift4G	Benign	0.44	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.10
MutPred		0.24		.;Gain of relative solvent accessibility (P = 0.0479);.;
MVP		0.082
MPC		0.32
ClinPred		0.072	T
GERP RS		3.5
Varity_R		0.10
gMVP		0.25
Mutation Taster		=83/17	polymorphism

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: rs772497737; hg19: chr1-159898300;