11-18709435-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_173588.4(IGSF22):āc.2950G>Cā(p.Gly984Arg) 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 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
IGSF22
NM_173588.4 missense
NM_173588.4 missense
Scores
4
5
8
Clinical Significance
Conservation
PhyloP100: 0.976
Genes affected
IGSF22 (HGNC:26750): (immunoglobulin superfamily member 22)
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ACMG classification
Classification made for transcript
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, 0.865
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IGSF22 | NM_173588.4 | c.2950G>C | p.Gly984Arg | missense_variant | 18/23 | ENST00000513874.6 | NP_775859.4 | |
IGSF22 | XM_047426830.1 | c.1024G>C | p.Gly342Arg | missense_variant | 5/10 | XP_047282786.1 | ||
IGSF22 | NR_160413.1 | n.2795G>C | non_coding_transcript_exon_variant | 17/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IGSF22 | ENST00000513874.6 | c.2950G>C | p.Gly984Arg | missense_variant | 18/23 | 5 | NM_173588.4 | ENSP00000421191 | P1 | |
IGSF22 | ENST00000504981.5 | n.3290G>C | non_coding_transcript_exon_variant | 17/20 | 1 | |||||
IGSF22-AS1 | ENST00000527285.1 | n.729+2042C>G | intron_variant, non_coding_transcript_variant | 3 | ||||||
IGSF22 | ENST00000319338.6 | c.2647G>C | p.Gly883Arg | missense_variant, NMD_transcript_variant | 17/21 | 2 | ENSP00000322422 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249546Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135394
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461878Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727240
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GnomAD4 genome Cov.: 32
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32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2023 | The c.2950G>C (p.G984R) alteration is located in exon 18 (coding exon 17) of the IGSF22 gene. This alteration results from a G to C substitution at nucleotide position 2950, causing the glycine (G) at amino acid position 984 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Pathogenic
D
Vest4
MutPred
Gain of MoRF binding (P = 0.0443);
MVP
MPC
ClinPred
D
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at