Variant chr1-159943127-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000368094.6(IGSF9):c.83C>T(p.Ser28Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000163 in 1,596,526 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: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

IGSF9
ENST00000368094.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.814

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IGSF9	NM_001135050.2 linkuse as main transcript	c.83C>T	p.Ser28Leu	missense_variant	3/21	ENST00000368094.6	NP_001128522.1
LOC124904438	XR_007066684.1 linkuse as main transcript	n.78+1681G>A		intron_variant, non_coding_transcript_variant
IGSF9	NM_020789.4 linkuse as main transcript	c.83C>T	p.Ser28Leu	missense_variant	3/21		NP_065840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF9	ENST00000368094.6 linkuse as main transcript	c.83C>T	p.Ser28Leu	missense_variant	3/21	1	NM_001135050.2	ENSP00000357073	P1	Q9P2J2-1
IGSF9	ENST00000361509.7 linkuse as main transcript	c.83C>T	p.Ser28Leu	missense_variant	3/21	1		ENSP00000355049		Q9P2J2-2
IGSF9	ENST00000476102.1 linkuse as main transcript	n.278C>T		non_coding_transcript_exon_variant	3/20	5

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000310

AC:

AN:

225954

Hom.:

AF XY:

0.0000243

AC XY:

AN XY:

123466

show subpopulations

Gnomad AFR exome

AF:

0.000135

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000120

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000290

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000145

AC:

AN:

1444458

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

718608

show subpopulations

Gnomad4 AFR exome

AF:

0.0000618

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000128

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000127

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152068

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2023

The c.83C>T (p.S28L) alteration is located in exon 3 (coding exon 2) of the IGSF9 gene. This alteration results from a C to T substitution at nucleotide position 83, causing the serine (S) at amino acid position 28 to be replaced by a leucine (L). 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

Benign

0.29

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.057

.;T;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.0090

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.29

N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.4

N;N;.

REVEL

Benign

0.083

Sift

Benign

0.13

T;T;.

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.0

.;B;.

Vest4

0.30

MVP

0.043

MPC

0.22

ClinPred

0.031

GERP RS

3.7

Varity_R

0.043

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: 24

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