chr11-18706090-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173588.4(IGSF22):​c.3637C>A​(p.Pro1213Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,548,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

IGSF22
NM_173588.4 missense

Scores

2
6
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31
Variant links:
Genes affected
IGSF22 (HGNC:26750): (immunoglobulin superfamily member 22)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.2632882).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IGSF22NM_173588.4 linkuse as main transcriptc.3637C>A p.Pro1213Thr missense_variant 22/23 ENST00000513874.6 NP_775859.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IGSF22ENST00000513874.6 linkuse as main transcriptc.3637C>A p.Pro1213Thr missense_variant 22/235 NM_173588.4 ENSP00000421191 P1Q8N9C0-2
IGSF22ENST00000510673.1 linkuse as main transcriptn.40C>A non_coding_transcript_exon_variant 1/23
IGSF22ENST00000319338.6 linkuse as main transcriptc.*533C>A 3_prime_UTR_variant, NMD_transcript_variant 20/212 ENSP00000322422 Q8N9C0-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152224
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:
0.000579
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000106
AC:
16
AN:
150276
Hom.:
0
AF XY:
0.000125
AC XY:
10
AN XY:
80102
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00139
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000233
GnomAD4 exome
AF:
0.0000158
AC:
22
AN:
1396274
Hom.:
0
Cov.:
32
AF XY:
0.0000189
AC XY:
13
AN XY:
688930
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000588
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000173
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152340
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000580
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000847
AC:
2
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsNov 09, 2023The c.3637C>A (p.P1213T) alteration is located in exon 22 (coding exon 21) of the IGSF22 gene. This alteration results from a C to A substitution at nucleotide position 3637, causing the proline (P) at amino acid position 1213 to be replaced by a threonine (T). 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
-0.34
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
23
DANN
Uncertain
0.99
Eigen
Uncertain
0.35
Eigen_PC
Benign
0.081
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.50
T
M_CAP
Uncertain
0.094
D
MetaRNN
Benign
0.26
T
MetaSVM
Uncertain
0.12
D
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.35
T
PROVEAN
Pathogenic
-6.7
D
REVEL
Uncertain
0.33
Sift
Uncertain
0.0080
D
Sift4G
Pathogenic
0.0
D
Vest4
0.38
MutPred
0.76
Gain of phosphorylation at P1213 (P = 0.0238);
MVP
0.57
MPC
0.78
ClinPred
0.36
T
GERP RS
3.9
gMVP
0.95

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: rs773108294; hg19: chr11-18727637; COSMIC: COSV55010210; COSMIC: COSV55010210; API