11-18707204-C-T

Position:

• chr11-18707204-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173588.4(IGSF22):​c.3290G>A​(p.Arg1097Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000873 in 1,374,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000087 (0 hom.)
• Consequence: IGSF22 NM_173588.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0320

Genes affected

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

IGSF22 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040451676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF22	NM_173588.4	c.3290G>A	p.Arg1097Gln	missense_variant	21/23	ENST00000513874.6	NP_775859.4
IGSF22	XM_047426830.1	c.1364G>A	p.Arg455Gln	missense_variant	8/10		XP_047282786.1
IGSF22	NR_160413.1	n.3046G>A		non_coding_transcript_exon_variant	19/21
IGSF22-AS1	NR_186353.1	n.669+55C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF22	ENST00000513874.6	c.3290G>A	p.Arg1097Gln	missense_variant	21/23	5	NM_173588.4	ENSP00000421191.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000873 AC: 12 AN: 1374722 Hom.: 0 Cov.: 32 AF XY: 0.00000593 AC XY: 4 AN XY: 674702

Gnomad4 AFR exome AF: 0.0000963

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: 0.00000658

Gnomad4 OTH exome AF: 0.0000352

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2024

The c.3290G>A (p.R1097Q) 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 3290, causing the arginine (R) at amino acid position 1097 to be replaced by a glutamine (Q). 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	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	17
DANN	Benign	0.83
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.96	T
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.024
Sift	Benign	0.77	T
Sift4G	Pathogenic	0.0	D
Vest4		0.063
MutPred		0.48		Loss of phosphorylation at T1100 (P = 0.0843);
MVP		0.067
MPC		0.26
ClinPred		0.042	T
GERP RS		-1.4
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs1229845079; hg19: chr11-18728751;