chr11-18707990-G-T

Variant names:

• chr11-18707990-G-T
• rs200008059
• NM_173588.4:c.3094C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173588.4(IGSF22):​c.3094C>A​(p.Pro1032Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: IGSF22 NM_173588.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.48

Genes affected

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

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

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.886

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF22	NM_173588.4	c.3094C>A	p.Pro1032Thr	missense_variant	Exon 20 of 23	ENST00000513874.6	NP_775859.4
IGSF22	XM_047426830.1	c.1168C>A	p.Pro390Thr	missense_variant	Exon 7 of 10		XP_047282786.1
IGSF22	NR_160413.1	n.2850C>A		non_coding_transcript_exon_variant	Exon 18 of 21
IGSF22-AS1	NR_186353.1	n.785+597G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF22	ENST00000513874.6	c.3094C>A	p.Pro1032Thr	missense_variant	Exon 20 of 23	5	NM_173588.4	ENSP00000421191.1
IGSF22	ENST00000504981.5	n.3434C>A		non_coding_transcript_exon_variant	Exon 19 of 20	1
IGSF22	ENST00000319338.6	n.2702C>A		non_coding_transcript_exon_variant	Exon 18 of 21	2		ENSP00000322422.6
IGSF22-AS1	ENST00000527285.1	n.729+597G>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1461728 Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13 AN XY: 727164

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000225

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	0.0034	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Benign	0.97
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.025	T
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.77	D
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0060	D
Sift4G	Pathogenic	0.0	D
Vest4		0.69
MutPred		0.72		Gain of phosphorylation at P1032 (P = 0.0668);
MVP		0.65
MPC		0.63
ClinPred		0.99	D
GERP RS		4.8
gMVP		0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs200008059; hg19: chr11-18729537;