Variant 11-18708289-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_173588.4(IGSF22):c.3005C>A(p.Pro1002His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000841 in 1,545,486 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

IGSF22
NM_173588.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.28

Variant links:

Genes affected

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

IGSF22 links:

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

IGSF22-AS1 links:

TMEM86A (HGNC:):

TMEM86A 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	UniProt
IGSF22	NM_173588.4 linkuse as main transcript	c.3005C>A	p.Pro1002His	missense_variant	19/23	ENST00000513874.6	NP_775859.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF22	ENST00000513874.6 linkuse as main transcript	c.3005C>A	p.Pro1002His	missense_variant	19/23	5	NM_173588.4	ENSP00000421191	P1	Q8N9C0-2
IGSF22	ENST00000504981.5 linkuse as main transcript	n.3345C>A		non_coding_transcript_exon_variant	18/20	1
IGSF22-AS1	ENST00000527285.1 linkuse as main transcript	n.729+896G>T		intron_variant, non_coding_transcript_variant		3
IGSF22	ENST00000319338.6 linkuse as main transcript	c.2696-293C>A		intron_variant, NMD_transcript_variant		2		ENSP00000322422		Q8N9C0-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000608

AC:

AN:

148022

Hom.:

AF XY:

0.0000768

AC XY:

AN XY:

78130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000379

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000861

AC:

AN:

1393292

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

686788

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000345

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000396

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

Dec 21, 2022

The c.3005C>A (p.P1002H) alteration is located in exon 19 (coding exon 18) of the IGSF22 gene. This alteration results from a C to A substitution at nucleotide position 3005, causing the proline (P) at amino acid position 1002 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

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.53

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-0.64

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-7.7

REVEL

Benign

0.24

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0

Vest4

0.59

MutPred

0.34

Loss of glycosylation at P1002 (P = 0.0166);

MVP

0.61

MPC

0.89

ClinPred

0.63

GERP RS

4.5

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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