chr11-18709437-A-T

Variant summary

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

The NM_173588.4(IGSF22):​c.2948T>A​(p.Val983Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

IGSF22
NM_173588.4 missense

Scores

1
1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.377
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19108632).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IGSF22NM_173588.4 linkuse as main transcriptc.2948T>A p.Val983Asp missense_variant 18/23 ENST00000513874.6 NP_775859.4
IGSF22XM_047426830.1 linkuse as main transcriptc.1022T>A p.Val341Asp missense_variant 5/10 XP_047282786.1
IGSF22NR_160413.1 linkuse as main transcriptn.2793T>A 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.2948T>A p.Val983Asp missense_variant 18/235 NM_173588.4 ENSP00000421191 P1Q8N9C0-2
IGSF22ENST00000504981.5 linkuse as main transcriptn.3288T>A non_coding_transcript_exon_variant 17/201
IGSF22-AS1ENST00000527285.1 linkuse as main transcriptn.729+2044A>T intron_variant, non_coding_transcript_variant 3
IGSF22ENST00000319338.6 linkuse as main transcriptc.2645T>A p.Val882Asp missense_variant, NMD_transcript_variant 17/212 ENSP00000322422 Q8N9C0-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151698
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:
0.000193
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
GnomAD3 exomes
AF:
0.0000200
AC:
5
AN:
249554
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135400
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000278
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461880
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151698
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74068
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2

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 GeneticsJun 16, 2023The c.2948T>A (p.V983D) alteration is located in exon 18 (coding exon 17) of the IGSF22 gene. This alteration results from a T to A substitution at nucleotide position 2948, causing the valine (V) at amino acid position 983 to be replaced by an aspartic acid (D). 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
0.44
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
20
DANN
Benign
0.96
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.084
N
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-0.91
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.67
N
REVEL
Benign
0.11
Sift
Benign
0.49
T
Sift4G
Pathogenic
0.0
D
Vest4
0.39
MutPred
0.51
Gain of disorder (P = 0.0144);
MVP
0.56
MPC
1.0
ClinPred
0.32
T
GERP RS
2.2
gMVP
0.49

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: rs766272943; hg19: chr11-18730984; API