1-159943410-G-C

Position:

• chr1-159943410-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000368094.6(IGSF9):​c.45C>G​(p.Ser15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,436,568 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IGSF9 ENST00000368094.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57

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]

LOC124904438 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19979957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF9	NM_001135050.2	c.45C>G	p.Ser15Arg	missense_variant	2/21	ENST00000368094.6	NP_001128522.1
LOC124904438	XR_007066684.1	n.78+1964G>C		intron_variant, non_coding_transcript_variant
IGSF9	NM_020789.4	c.45C>G	p.Ser15Arg	missense_variant	2/21		NP_065840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF9	ENST00000368094.6	c.45C>G	p.Ser15Arg	missense_variant	2/21	1	NM_001135050.2	ENSP00000357073	P1
IGSF9	ENST00000361509.7	c.45C>G	p.Ser15Arg	missense_variant	2/21	1		ENSP00000355049
IGSF9	ENST00000476102.1	n.240C>G		non_coding_transcript_exon_variant	2/20	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1436568 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 712290

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: 0.0000244

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.45C>G (p.S15R) alteration is located in exon 2 (coding exon 1) of the IGSF9 gene. This alteration results from a C to G substitution at nucleotide position 45, causing the serine (S) at amino acid position 15 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	0.66
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	.;T;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.8	L;L;.
MutationTaster	Benign	0.80	N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.7	N;N;.
REVEL	Benign	0.20
Sift	Uncertain	0.029	D;D;.
Sift4G	Uncertain	0.047	D;D;T
Polyphen		1.0	.;D;.
Vest4		0.29
MutPred		0.61		Gain of MoRF binding (P = 0.0199);Gain of MoRF binding (P = 0.0199);Gain of MoRF binding (P = 0.0199);
MVP		0.068
MPC		0.29
ClinPred		0.68	D
GERP RS		3.9
Varity_R		0.19
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1242513313; hg19: chr1-159913200;