rs1229845079

Variant names:

• chr11-18707204-C-T
• rs1229845079
• NM_173588.4:c.3290G>A

Variant summary

Our verdict is Likely benign. The variant received -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 0 publications found

Genes affected

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

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173588.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF22	NM_173588.4	MANE Select	c.3290G>A	p.Arg1097Gln	missense	Exon 21 of 23	NP_775859.4	Q8N9C0-2
	IGSF22	NR_160413.1		n.3046G>A		non_coding_transcript_exon	Exon 19 of 21
	IGSF22-AS1	NR_186353.1		n.669+55C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF22	ENST00000513874.6	TSL:5 MANE Select	c.3290G>A	p.Arg1097Gln	missense	Exon 21 of 23	ENSP00000421191.1	Q8N9C0-2
	IGSF22	ENST00000504981.5	TSL:1	n.3630G>A		non_coding_transcript_exon	Exon 20 of 20
	IGSF22	ENST00000319338.6	TSL:2	n.*186G>A		non_coding_transcript_exon	Exon 19 of 21	ENSP00000322422.6	Q8N9C0-1

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

African (AFR) AF: 0.0000963 AC: 3 AN: 31158

American (AMR) AF: 0.00 AC: 0 AN: 33432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23902

East Asian (EAS) AF: 0.00 AC: 0 AN: 35320

South Asian (SAS) AF: 0.00 AC: 0 AN: 76090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5586

European-Non Finnish (NFE) AF: 0.00000658 AC: 7 AN: 1063982

Other (OTH) AF: 0.0000352 AC: 2 AN: 56894

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
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
PhyloP100		0.032
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
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1229845079; hg19: chr11-18728751;