11-18707198-G-A

Variant names:

• chr11-18707198-G-A
• rs528788256
• NM_173588.4:c.3296C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_173588.4(IGSF22):​c.3296C>T​(p.Pro1099Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000259 in 1,532,310 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1099R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: IGSF22 NM_173588.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019312352).

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.3296C>T	p.Pro1099Leu	missense	Exon 21 of 23	NP_775859.4	Q8N9C0-2
	IGSF22	NR_160413.1		n.3052C>T		non_coding_transcript_exon	Exon 19 of 21
	IGSF22-AS1	NR_186353.1		n.669+49G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF22	ENST00000513874.6	TSL:5 MANE Select	c.3296C>T	p.Pro1099Leu	missense	Exon 21 of 23	ENSP00000421191.1	Q8N9C0-2
	IGSF22	ENST00000504981.5	TSL:1	n.3636C>T		non_coding_transcript_exon	Exon 20 of 20
	IGSF22	ENST00000319338.6	TSL:2	n.*192C>T		non_coding_transcript_exon	Exon 19 of 21	ENSP00000322422.6	Q8N9C0-1

Frequencies

GnomAD3 genomes AF: 0.00150 AC: 229 AN: 152162 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00545

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000313 AC: 44 AN: 140596 AF XY: 0.000189

Gnomad AFR exome AF: 0.00524

Gnomad AMR exome AF: 0.000131

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000122 AC: 168 AN: 1380032 Hom.: 0 Cov.: 32 AF XY: 0.000105 AC XY: 71 AN XY: 677852

African (AFR) AF: 0.00477 AC: 149 AN: 31252

American (AMR) AF: 0.000118 AC: 4 AN: 33962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24220

East Asian (EAS) AF: 0.00 AC: 0 AN: 35404

South Asian (SAS) AF: 0.00 AC: 0 AN: 76912

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 9.37e-7 AC: 1 AN: 1066906

Other (OTH) AF: 0.000245 AC: 14 AN: 57156

GnomAD4 genome AF: 0.00150 AC: 229 AN: 152278 Hom.: 1 Cov.: 32 AF XY: 0.00146 AC XY: 109 AN XY: 74464

African (AFR) AF: 0.00544 AC: 226 AN: 41550

American (AMR) AF: 0.000131 AC: 2 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.00148 Hom.: 0

Bravo AF: 0.00139

ExAC AF: 0.000565 AC: 13

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.019	T
MetaSVM	Uncertain	0.44	D
PhyloP100		2.9
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-9.1	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Vest4		0.63
MVP		0.68
MPC		0.23
ClinPred		0.20	T
GERP RS		4.1
gMVP		0.79
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs528788256; hg19: chr11-18728745;