Variant 11-18706968-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_173588.4(IGSF22):c.3526G>A(p.Gly1176Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000288 in 1,389,242 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: not found (cov: 31)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

IGSF22
NM_173588.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.966

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF22	NM_173588.4 linkuse as main transcript	c.3526G>A	p.Gly1176Ser	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.3526G>A	p.Gly1176Ser	missense_variant	21/23	5	NM_173588.4	ENSP00000421191	P1	Q8N9C0-2
IGSF22-AS1	ENST00000527285.1 linkuse as main transcript	n.432C>T		non_coding_transcript_exon_variant	1/3	3
IGSF22	ENST00000319338.6 linkuse as main transcript	c.*422G>A		3_prime_UTR_variant, NMD_transcript_variant	19/21	2		ENSP00000322422		Q8N9C0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000687

AC:

AN:

145542

Hom.:

AF XY:

0.00

AC XY:

AN XY:

76644

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000288

AC:

AN:

1389242

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

684006

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000186

Gnomad4 OTH exome

AF:

0.0000347

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

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

Jan 27, 2022

The c.3526G>A (p.G1176S) alteration is located in exon 21 (coding exon 20) of the IGSF22 gene. This alteration results from a G to A substitution at nucleotide position 3526, causing the glycine (G) at amino acid position 1176 to be replaced by a serine (S). 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

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.34

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.64

M_CAP

Benign

0.067

MetaRNN

Pathogenic

0.97

MetaSVM

Benign

-0.71

MutationTaster

Benign

0.98

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-5.4

REVEL

Benign

0.20

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.66

MutPred

0.91

Gain of disorder (P = 0.0752);

MVP

0.42

MPC

0.83

ClinPred

0.96

GERP RS

1.8

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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