Variant chr11-18709435-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_173588.4(IGSF22):c.2950G>C(p.Gly984Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 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: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IGSF22
NM_173588.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.976

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 made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.865

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IGSF22	NM_173588.4 linkuse as main transcript	c.2950G>C	p.Gly984Arg	missense_variant	18/23	ENST00000513874.6	NP_775859.4
IGSF22	XM_047426830.1 linkuse as main transcript	c.1024G>C	p.Gly342Arg	missense_variant	5/10		XP_047282786.1
IGSF22	NR_160413.1 linkuse as main transcript	n.2795G>C		non_coding_transcript_exon_variant	17/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF22	ENST00000513874.6 linkuse as main transcript	c.2950G>C	p.Gly984Arg	missense_variant	18/23	5	NM_173588.4	ENSP00000421191	P1	Q8N9C0-2
IGSF22	ENST00000504981.5 linkuse as main transcript	n.3290G>C		non_coding_transcript_exon_variant	17/20	1
IGSF22-AS1	ENST00000527285.1 linkuse as main transcript	n.729+2042C>G		intron_variant, non_coding_transcript_variant		3
IGSF22	ENST00000319338.6 linkuse as main transcript	c.2647G>C	p.Gly883Arg	missense_variant, NMD_transcript_variant	17/21	2		ENSP00000322422		Q8N9C0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249546

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135394

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:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727240

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

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

Mar 07, 2023

The c.2950G>C (p.G984R) alteration is located in exon 18 (coding exon 17) of the IGSF22 gene. This alteration results from a G to C substitution at nucleotide position 2950, causing the glycine (G) at amino acid position 984 to be replaced by an arginine (R). 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

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.20

Eigen_PC

Benign

-0.029

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.77

M_CAP

Benign

0.033

MetaRNN

Pathogenic

0.86

MetaSVM

Benign

-0.64

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-4.4

REVEL

Uncertain

0.32

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Vest4

0.51

MutPred

0.84

Gain of MoRF binding (P = 0.0443);

MVP

0.64

MPC

0.92

ClinPred

0.95

GERP RS

0.35

gMVP

0.84

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