Variant 11-18707000-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_173588.4(IGSF22):c.3494A>G(p.Tyr1165Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000587 in 1,551,032 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 0.000092 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

IGSF22
NM_173588.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.85

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22486177).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF22	NM_173588.4 linkuse as main transcript	c.3494A>G	p.Tyr1165Cys	missense_variant	21/23	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.3494A>G	p.Tyr1165Cys	missense_variant	21/23	5	NM_173588.4	ENSP00000421191	P1	Q8N9C0-2
IGSF22-AS1	ENST00000527285.1 linkuse as main transcript	n.464T>C		non_coding_transcript_exon_variant	1/3	3
IGSF22	ENST00000319338.6 linkuse as main transcript	c.*390A>G		3_prime_UTR_variant, NMD_transcript_variant	19/21	2		ENSP00000322422		Q8N9C0-1
IGSF22	ENST00000504981.5 linkuse as main transcript			downstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00259

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

GnomAD3 exomes

AF:

0.000215

AC:

AN:

153222

Hom.:

AF XY:

0.000258

AC XY:

AN XY:

81260

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000813

Gnomad ASJ exome

AF:

0.00320

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000338

Gnomad OTH exome

AF:

0.000463

GnomAD4 exome

AF:

0.0000550

AC:

AN:

1398834

Hom.:

Cov.:

AF XY:

0.0000522

AC XY:

AN XY:

689906

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00227

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000742

Gnomad4 OTH exome

AF:

0.000121

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000383

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.000421

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

Feb 28, 2023

The c.3494A>G (p.Y1165C) alteration is located in exon 21 (coding exon 20) of the IGSF22 gene. This alteration results from a A to G substitution at nucleotide position 3494, causing the tyrosine (Y) at amino acid position 1165 to be replaced by a cysteine (C). 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

-0.051

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.62

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.22

MetaSVM

Uncertain

0.30

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-8.3

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.78

MVP

0.64

MPC

0.93

ClinPred

0.54

GERP RS

2.6

gMVP

0.89

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