NM_173588.4:c.2980C>G

Variant names:

• chr11-18709405-G-C
• NM_173588.4:c.2980C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173588.4(IGSF22):​c.2980C>G​(p.Arg994Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: IGSF22 NM_173588.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.626

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12908831).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF22	NM_173588.4	c.2980C>G	p.Arg994Gly	missense_variant	Exon 18 of 23	ENST00000513874.6	NP_775859.4
IGSF22	XM_047426830.1	c.1054C>G	p.Arg352Gly	missense_variant	Exon 5 of 10		XP_047282786.1
IGSF22	NR_160413.1	n.2825C>G		non_coding_transcript_exon_variant	Exon 17 of 21
IGSF22-AS1	NR_186353.1	n.785+2012G>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF22	ENST00000513874.6	c.2980C>G	p.Arg994Gly	missense_variant	Exon 18 of 23	5	NM_173588.4	ENSP00000421191.1
IGSF22	ENST00000504981.5	n.3320C>G		non_coding_transcript_exon_variant	Exon 17 of 20	1
IGSF22	ENST00000319338.6	n.2677C>G		non_coding_transcript_exon_variant	Exon 17 of 21	2		ENSP00000322422.6
IGSF22-AS1	ENST00000527285.1	n.729+2012G>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461618 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727122

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Uncertain	0.99
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.031
Sift	Benign	0.40	T
Sift4G	Uncertain	0.056	T
Vest4		0.20
MutPred		0.39		Gain of ubiquitination at K991 (P = 0.041);
MVP		0.44
MPC		0.31
ClinPred		0.21	T
GERP RS		2.7
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-18730952;