rs10832975

Positions:

• chr11-18721633-C-A
• chr11-18721633-C-G
• chr11-18721633-C-T

Variant summary

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

The NM_173588.4(IGSF22):​c.280G>T​(p.Ala94Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A94P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IGSF22 NM_173588.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.57

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=0.24588665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF22	NM_173588.4	c.280G>T	p.Ala94Ser	missense_variant	4/23	ENST00000513874.6	NP_775859.4
IGSF22	NR_160413.1	n.428G>T		non_coding_transcript_exon_variant	4/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF22	ENST00000513874.6	c.280G>T	p.Ala94Ser	missense_variant	4/23	5	NM_173588.4	ENSP00000421191	P1
IGSF22	ENST00000504981.5	n.421G>T		non_coding_transcript_exon_variant	4/20	1
IGSF22-AS1	ENST00000527285.1	n.729+14240C>A		intron_variant, non_coding_transcript_variant		3
IGSF22	ENST00000319338.6	c.280G>T	p.Ala94Ser	missense_variant, NMD_transcript_variant	4/21	2		ENSP00000322422

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.090
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.23	T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.77	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.15
Sift	Benign	0.036	D
Sift4G	Uncertain	0.045	D
Vest4		0.18
MutPred		0.65		Gain of disorder (P = 0.0358);
MVP		0.72
MPC		0.23
ClinPred		0.99	D
GERP RS		4.4
gMVP		0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs10832975; hg19: chr11-18743180;