11-18707012-G-C

Position:

• chr11-18707012-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_173588.4(IGSF22):​c.3482C>G​(p.Pro1161Arg) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: IGSF22 NM_173588.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.48

Genes affected

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

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

TMEM86A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.758

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF22	NM_173588.4	c.3482C>G	p.Pro1161Arg	missense_variant	21/23	ENST00000513874.6	NP_775859.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF22	ENST00000513874.6	c.3482C>G	p.Pro1161Arg	missense_variant	21/23	5	NM_173588.4	ENSP00000421191	P1
IGSF22-AS1	ENST00000527285.1	n.476G>C		non_coding_transcript_exon_variant	1/3	3
IGSF22	ENST00000319338.6	c.*378C>G		3_prime_UTR_variant, NMD_transcript_variant	19/21	2		ENSP00000322422
IGSF22	ENST00000504981.5			downstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

AiLife Diagnostics, AiLife Diagnostics

Jul 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.40	T
MutationTaster	Benign	0.98	N
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-7.8	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0060	D
Sift4G	Pathogenic	0.0	D
Vest4		0.57
MutPred		0.69		Gain of MoRF binding (P = 8e-04);
MVP		0.64
MPC		0.84
ClinPred		0.98	D
GERP RS		3.4
gMVP		0.37

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: chr11-18728559;