Genetic Variant IGSF11:p.Pro418Arg (chr3-118902563-G-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001015887.3(IGSF11):c.1253C>G(p.Pro418Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000163 in 1,599,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

IGSF11
NM_001015887.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.13

Publications

0 publications found

Variant links:

Genes affected

IGSF11 (HGNC:16669): (immunoglobulin superfamily member 11) IGSF11 is an immunoglobulin (Ig) superfamily member that is preferentially expressed in brain and testis. It shares significant homology with coxsackievirus and adenovirus receptor (CXADR; MIM 602621) and endothelial cell-selective adhesion molecule (ESAM).[supplied by OMIM, Apr 2005]

IGSF11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.866

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001015887.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGSF11	NM_001015887.3	MANE Select	c.1253C>G	p.Pro418Arg	missense	Exon 7 of 7	NP_001015887.1	Q5DX21-1
IGSF11	NM_001353318.2		c.1403C>G	p.Pro468Arg	missense	Exon 8 of 8	NP_001340247.1
IGSF11	NM_001353319.2		c.1319C>G	p.Pro440Arg	missense	Exon 8 of 8	NP_001340248.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGSF11	ENST00000393775.7	TSL:1 MANE Select	c.1253C>G	p.Pro418Arg	missense	Exon 7 of 7	ENSP00000377370.2	Q5DX21-1
IGSF11	ENST00000354673.6	TSL:1	c.1250C>G	p.Pro417Arg	missense	Exon 7 of 7	ENSP00000346700.2	Q5DX21-2
IGSF11	ENST00000874675.1		c.1403C>G	p.Pro468Arg	missense	Exon 8 of 8	ENSP00000544734.1

Frequencies

GnomAD3 genomes

AF:

0.00000667

AC:

AN:

149990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251254

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1449424

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

720858

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33090

American (AMR)

AF:

0.00

AC:

AN:

44362

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25688

East Asian (EAS)

AF:

0.00

AC:

AN:

39002

South Asian (SAS)

AF:

0.00

AC:

AN:

86126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.0000227

AC:

AN:

1103420

Other (OTH)

AF:

0.00

AC:

AN:

59532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000667

AC:

AN:

149990

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73080

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40836

American (AMR)

AF:

0.00

AC:

AN:

14940

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

4946

South Asian (SAS)

AF:

0.00

AC:

AN:

4692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10150

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67694

Other (OTH)

AF:

0.00

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000313

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Pathogenic

0.44

BayesDel_noAF

Pathogenic

0.42

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.20

MetaRNN

Pathogenic

0.87

MetaSVM

Pathogenic

0.81

MutationAssessor

Uncertain

2.1

PhyloP100

9.1

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-5.1

REVEL

Pathogenic

0.84

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.86

MVP

0.90

MPC

1.1

ClinPred

0.99

GERP RS

5.0

Varity_R

0.69

gMVP

0.72

Mutation Taster

=16/84

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over