rs371199923

Variant names:

• chr11-18707190-G-T
• rs371199923
• NM_173588.4:c.3304C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-18707190-G-T
• chr11-18707190-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173588.4(IGSF22):​c.3304C>A​(p.Leu1102Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 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: 7.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IGSF22 NM_173588.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.161
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09625444).

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.3304C>A	p.Leu1102Ile	missense	Exon 21 of 23	NP_775859.4	Q8N9C0-2
	IGSF22	NR_160413.1		n.3060C>A		non_coding_transcript_exon	Exon 19 of 21
	IGSF22-AS1	NR_186353.1		n.669+41G>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.3304C>A	p.Leu1102Ile	missense	Exon 21 of 23	ENSP00000421191.1	Q8N9C0-2
	IGSF22	ENST00000504981.5	TSL:1	n.3644C>A		non_coding_transcript_exon	Exon 20 of 20
	IGSF22	ENST00000319338.6	TSL:2	n.*200C>A		non_coding_transcript_exon	Exon 19 of 21	ENSP00000322422.6	Q8N9C0-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000690 AC: 1 AN: 144880 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000931

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.22e-7 AC: 1 AN: 1385976 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 681768

African (AFR) AF: 0.00 AC: 0 AN: 31338

American (AMR) AF: 0.00 AC: 0 AN: 34296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24552

East Asian (EAS) AF: 0.0000282 AC: 1 AN: 35484

South Asian (SAS) AF: 0.00 AC: 0 AN: 77732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5660

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1070636

Other (OTH) AF: 0.00 AC: 0 AN: 57422

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.27
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Benign	0.83
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.16
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.83	N
REVEL	Benign	0.071
Sift	Benign	0.78	T
Sift4G	Benign	0.24	T
Vest4		0.23
MutPred		0.56		Loss of loop (P = 0.1242)
MVP		0.33
MPC		0.73
ClinPred		0.13	T
GERP RS		3.2
gMVP		0.16
Mutation Taster		=98/2	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: rs371199923; hg19: chr11-18728737;