11-18707854-A-C

Position:

• chr11-18707854-A-C

Variant summary

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

The NM_173588.4(IGSF22):​c.3230T>G​(p.Leu1077Arg) variant causes a missense change. 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: 33)
• Consequence: IGSF22 NM_173588.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.03

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.88

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGSF22	NM_173588.4	c.3230T>G	p.Leu1077Arg	missense_variant	20/23	ENST00000513874.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF22	ENST00000513874.6	c.3230T>G	p.Leu1077Arg	missense_variant	20/23	5	NM_173588.4	P1
IGSF22	ENST00000504981.5	n.3570T>G		non_coding_transcript_exon_variant	19/20	1
IGSF22-AS1	ENST00000527285.1	n.729+461A>C		intron_variant, non_coding_transcript_variant		3
IGSF22	ENST00000319338.6	c.*126T>G		3_prime_UTR_variant, NMD_transcript_variant	18/21	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Jan 31, 2023

The c.3230T>G (p.L1077R) alteration is located in exon 20 (coding exon 19) of the IGSF22 gene. This alteration results from a T to G substitution at nucleotide position 3230, causing the leucine (L) at amino acid position 1077 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	0.0044	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.52	T
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.50	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0090	D
Vest4		0.86
MutPred		0.70		Gain of MoRF binding (P = 0.0168);
MVP		0.64
MPC		1.0
ClinPred		0.98	D
GERP RS		3.8
gMVP		0.84

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: chr11-18729401;