1-159943061-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001135050.2(IGSF9):c.149C>A(p.Pro50His) variant causes a missense change. The variant allele was found at a frequency of 0.000261 in 1,611,658 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P50L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 1 hom. )

Consequence

IGSF9
NM_001135050.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.58

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:

LOC124904438 (HGNC:):

LOC124904438 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.13479605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF9	NM_001135050.2 link	c.149C>A	p.Pro50His	missense_variant	Exon 3 of 21	ENST00000368094.6	NP_001128522.1	Q9P2J2-1
IGSF9	NM_020789.4 link	c.149C>A	p.Pro50His	missense_variant	Exon 3 of 21		NP_065840.2	Q9P2J2-2
LOC124904438	XR_007066684.1 link	n.78+1615G>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IGSF9	ENST00000368094.6 link	c.149C>A	p.Pro50His	missense_variant	Exon 3 of 21	1	NM_001135050.2	ENSP00000357073.1	Q9P2J2-1
IGSF9	ENST00000361509.7 link	c.149C>A	p.Pro50His	missense_variant	Exon 3 of 21	1		ENSP00000355049.3	Q9P2J2-2
IGSF9	ENST00000476102.1 link	n.344C>A		non_coding_transcript_exon_variant	Exon 3 of 20	5

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000281

AC:

AN:

245680

Hom.:

AF XY:

0.000345

AC XY:

AN XY:

133376

show subpopulations

Gnomad AFR exome

AF:

0.000380

Gnomad AMR exome

AF:

0.0000589

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000607

Gnomad SAS exome

AF:

0.00122

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000100

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

AF:

0.000269

AC:

393

AN:

1459480

Hom.:

Cov.:

AF XY:

0.000343

AC XY:

249

AN XY:

726020

show subpopulations

Gnomad4 AFR exome

AF:

0.000300

Gnomad4 AMR exome

AF:

0.0000451

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000329

Gnomad4 SAS exome

AF:

0.00150

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000206

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000177

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000127

Hom.:

Bravo

AF:

0.000200

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000305

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.149C>A (p.P50H) alteration is located in exon 3 (coding exon 2) of the IGSF9 gene. This alteration results from a C to A substitution at nucleotide position 149, causing the proline (P) at amino acid position 50 to be replaced by a histidine (H). 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

Uncertain

0.34

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

.;T;T

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.050

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.4

M;M;.

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-4.4

D;D;.

REVEL

Uncertain

0.40

Sift

Uncertain

0.0020

D;D;.

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.67

MVP

0.17

MPC

0.95

ClinPred

0.35

GERP RS

4.8

Varity_R

0.34

gMVP

0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over