chr11-18709494-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_173588.4(IGSF22):​c.2891G>T​(p.Gly964Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,614,098 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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

IGSF22
NM_173588.4 missense

Scores

2
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.28
Variant links:
Genes affected
IGSF22 (HGNC:26750): (immunoglobulin superfamily member 22)
IGSF22-AS1 (HGNC:55511): (IGSF22 antisense RNA 1)

Genome browser will be placed here

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, 0.898

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IGSF22NM_173588.4 linkuse as main transcriptc.2891G>T p.Gly964Val missense_variant 18/23 ENST00000513874.6 NP_775859.4
IGSF22XM_047426830.1 linkuse as main transcriptc.965G>T p.Gly322Val missense_variant 5/10 XP_047282786.1
IGSF22NR_160413.1 linkuse as main transcriptn.2736G>T non_coding_transcript_exon_variant 17/21

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IGSF22ENST00000513874.6 linkuse as main transcriptc.2891G>T p.Gly964Val missense_variant 18/235 NM_173588.4 ENSP00000421191 P1Q8N9C0-2
IGSF22ENST00000504981.5 linkuse as main transcriptn.3231G>T non_coding_transcript_exon_variant 17/201
IGSF22-AS1ENST00000527285.1 linkuse as main transcriptn.729+2101C>A intron_variant, non_coding_transcript_variant 3
IGSF22ENST00000319338.6 linkuse as main transcriptc.2588G>T p.Gly863Val missense_variant, NMD_transcript_variant 17/212 ENSP00000322422 Q8N9C0-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152208
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461890
Hom.:
0
Cov.:
34
AF XY:
0.0000110
AC XY:
8
AN XY:
727248
show subpopulations
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:
0.0000144
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152208
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

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 submitterclinical testingAmbry GeneticsSep 20, 2023The c.2891G>T (p.G964V) alteration is located in exon 18 (coding exon 17) of the IGSF22 gene. This alteration results from a G to T substitution at nucleotide position 2891, causing the glycine (G) at amino acid position 964 to be replaced by a valine (V). 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
AlphaMissense
Uncertain
0.37
BayesDel_addAF
Uncertain
0.013
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
21
DANN
Uncertain
1.0
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.61
T
M_CAP
Benign
0.046
D
MetaRNN
Pathogenic
0.90
D
MetaSVM
Uncertain
-0.18
T
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.37
T
PROVEAN
Pathogenic
-8.2
D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0080
D
Vest4
0.69
MutPred
0.76
Gain of MoRF binding (P = 0.1295);
MVP
0.68
MPC
0.34
ClinPred
1.0
D
GERP RS
2.4
gMVP
0.73

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs972906370; hg19: chr11-18731041; API