Genetic Variant IGSF22:p.Pro1099Arg (chr11-18707198-G-C) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_173588.4(IGSF22):c.3296C>G(p.Pro1099Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000457 in 1,532,194 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

IGSF22
NM_173588.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.94

Publications

1 publications found

Variant links:

Genes affected

IGSF22 (HGNC:26750): (immunoglobulin superfamily member 22)

IGSF22 links:

IGSF22-AS1 (HGNC:55511): (IGSF22 antisense RNA 1)

IGSF22-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.982

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173588.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGSF22	NM_173588.4	MANE Select	c.3296C>G	p.Pro1099Arg	missense	Exon 21 of 23	NP_775859.4	Q8N9C0-2
IGSF22	NR_160413.1		n.3052C>G		non_coding_transcript_exon	Exon 19 of 21
IGSF22-AS1	NR_186353.1		n.669+49G>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGSF22	ENST00000513874.6	TSL:5 MANE Select	c.3296C>G	p.Pro1099Arg	missense	Exon 21 of 23	ENSP00000421191.1	Q8N9C0-2
IGSF22	ENST00000504981.5	TSL:1	n.3636C>G		non_coding_transcript_exon	Exon 20 of 20
IGSF22	ENST00000319338.6	TSL:2	n.*192C>G		non_coding_transcript_exon	Exon 19 of 21	ENSP00000322422.6	Q8N9C0-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152162

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000435

AC:

AN:

1380032

Hom.:

Cov.:

AF XY:

0.00000443

AC XY:

AN XY:

677852

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31252

American (AMR)

AF:

0.00

AC:

AN:

33962

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24220

East Asian (EAS)

AF:

0.00

AC:

AN:

35404

South Asian (SAS)

AF:

0.00

AC:

AN:

76912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5624

European-Non Finnish (NFE)

AF:

0.00000562

AC:

AN:

1066906

Other (OTH)

AF:

0.00

AC:

AN:

57156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

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:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41430

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

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

0.99

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.60

M_CAP

Benign

0.060

MetaRNN

Pathogenic

0.98

MetaSVM

Uncertain

0.45

PhyloP100

2.9

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-8.2

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Vest4

0.66

MutPred

0.87

Loss of catalytic residue at P1098 (P = 0.0138)

MVP

0.64

MPC

0.24

ClinPred

0.95

GERP RS

4.1

gMVP

0.82

Mutation Taster

=77/23

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over