chr11-18707166-T-C

Variant names:

• chr11-18707166-T-C
• NM_173588.4:c.3328A>G

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.3328A>G​(p.Asn1110Asp) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IGSF22 NM_173588.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.62
• 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=0.12187472).

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.3328A>G	p.Asn1110Asp	missense	Exon 21 of 23	NP_775859.4	Q8N9C0-2
	IGSF22	NR_160413.1		n.3084A>G		non_coding_transcript_exon	Exon 19 of 21
	IGSF22-AS1	NR_186353.1		n.669+17T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF22	ENST00000513874.6	TSL:5 MANE Select	c.3328A>G	p.Asn1110Asp	missense	Exon 21 of 23	ENSP00000421191.1	Q8N9C0-2
	IGSF22	ENST00000504981.5	TSL:1	n.3668A>G		non_coding_transcript_exon	Exon 20 of 20
	IGSF22	ENST00000319338.6	TSL:2	n.*224A>G		non_coding_transcript_exon	Exon 19 of 21	ENSP00000322422.6	Q8N9C0-1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152292 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74464

African (AFR) AF: 0.00 AC: 0 AN: 41556

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2112

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	0.30
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	22
DANN	Benign	0.97
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.6
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.10
Sift	Benign	0.33	T
Sift4G	Benign	0.20	T
Vest4		0.26
MutPred		0.56		Gain of phosphorylation at T1111 (P = 0.1319)
MVP		0.28
MPC		0.31
ClinPred		0.18	T
GERP RS		3.0
gMVP		0.27
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr11-18728713;