NM_173588.4:c.3637C>T

Variant names:

• chr11-18706090-G-A
• rs773108294
• NM_173588.4:c.3637C>T

Variant summary

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

The NM_173588.4(IGSF22):​c.3637C>T​(p.Pro1213Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000194 in 1,548,500 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P1213T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IGSF22 NM_173588.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.3637C>T	p.Pro1213Ser	missense	Exon 22 of 23	NP_775859.4	Q8N9C0-2
	IGSF22	NR_160413.1		n.3393C>T		non_coding_transcript_exon	Exon 20 of 21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF22	ENST00000513874.6	TSL:5 MANE Select	c.3637C>T	p.Pro1213Ser	missense	Exon 22 of 23	ENSP00000421191.1	Q8N9C0-2
	IGSF22	ENST00000319338.6	TSL:2	n.*533C>T		non_coding_transcript_exon	Exon 20 of 21	ENSP00000322422.6	Q8N9C0-1
	IGSF22	ENST00000510673.1	TSL:3	n.40C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152224 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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1396276 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 688930

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25162

East Asian (EAS) AF: 0.00 AC: 0 AN: 35730

South Asian (SAS) AF: 0.00 AC: 0 AN: 79204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078838

Other (OTH) AF: 0.00 AC: 0 AN: 57968

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74368

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Uncertain	0.35
Eigen_PC	Benign	0.078
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Uncertain	0.12	D
PhyloP100		2.3
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.012	D
Sift4G	Pathogenic	0.0	D
Vest4		0.42
MVP		0.52
MPC		0.70
ClinPred		0.88	D
GERP RS		3.9
gMVP		0.95
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: rs773108294; hg19: chr11-18727637;