11-18708262-T-C

Position:

• chr11-18708262-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173588.4(IGSF22):​c.3032A>G​(p.Lys1011Arg) 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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IGSF22 NM_173588.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31395084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF22	NM_173588.4	c.3032A>G	p.Lys1011Arg	missense_variant	19/23	ENST00000513874.6	NP_775859.4
IGSF22	XM_047426830.1	c.1106A>G	p.Lys369Arg	missense_variant	6/10		XP_047282786.1
IGSF22	NR_160413.1	n.2844-266A>G		intron_variant
IGSF22-AS1	NR_186353.1	n.785+869T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF22	ENST00000513874.6	c.3032A>G	p.Lys1011Arg	missense_variant	19/23	5	NM_173588.4	ENSP00000421191.1
IGSF22	ENST00000504981.5	n.3372A>G		non_coding_transcript_exon_variant	18/20	1
IGSF22	ENST00000319338.6	n.2696-266A>G		intron_variant		2		ENSP00000322422.6
IGSF22-AS1	ENST00000527285.1	n.729+869T>C		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1396602 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 688672

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 07, 2024

The c.3032A>G (p.K1011R) alteration is located in exon 19 (coding exon 18) of the IGSF22 gene. This alteration results from a A to G substitution at nucleotide position 3032, causing the lysine (K) at amino acid position 1011 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.97	T
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.10
Sift	Benign	0.094	T
Sift4G	Pathogenic	0.0	D
Vest4		0.29
MutPred		0.40		Loss of ubiquitination at K1011 (P = 0.0224);
MVP		0.48
MPC		0.75
ClinPred		0.96	D
GERP RS		4.3
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: chr11-18729809;