chr1-18365334-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032880.5(IGSF21):​c.652C>T​(p.Arg218Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

IGSF21
NM_032880.5 missense

Scores

2
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53
Variant links:
Genes affected
IGSF21 (HGNC:28246): (immunoglobin superfamily member 21) This gene encodes a protein which has two immunoglobulin (Ig) domains and is a member of the immunoglobulin superfamily. Proteins in this superfamily are usually found on or in cell membranes and act as receptors in immune response pathways. [provided by RefSeq, Sep 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IGSF21NM_032880.5 linkc.652C>T p.Arg218Cys missense_variant Exon 6 of 10 ENST00000251296.4 NP_116269.3 Q96ID5
IGSF21XM_017002604.3 linkc.634C>T p.Arg212Cys missense_variant Exon 6 of 10 XP_016858093.1
IGSF21XM_017002605.1 linkc.421C>T p.Arg141Cys missense_variant Exon 5 of 9 XP_016858094.1
IGSF21XM_011542319.4 linkc.425-10976C>T intron_variant Intron 4 of 7 XP_011540621.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IGSF21ENST00000251296.4 linkc.652C>T p.Arg218Cys missense_variant Exon 6 of 10 1 NM_032880.5 ENSP00000251296.1 Q96ID5
IGSF21ENST00000412684.3 linkn.509C>T non_coding_transcript_exon_variant Exon 5 of 6 5
IGSF21ENST00000497331.2 linkn.976C>T non_coding_transcript_exon_variant Exon 2 of 6 2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152128
Hom.:
0
Cov.:
31
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251274
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135868
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000219
AC:
32
AN:
1461878
Hom.:
0
Cov.:
32
AF XY:
0.0000179
AC XY:
13
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000261
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152128
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74310
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000450
Hom.:
0
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
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
Dec 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.652C>T (p.R218C) alteration is located in exon 6 (coding exon 6) of the IGSF21 gene. This alteration results from a C to T substitution at nucleotide position 652, causing the arginine (R) at amino acid position 218 to be replaced by a cysteine (C). 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
0.39
BayesDel_addAF
Uncertain
0.052
T
BayesDel_noAF
Uncertain
-0.060
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.042
T
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.076
D
MetaRNN
Uncertain
0.65
D
MetaSVM
Benign
-0.58
T
MutationAssessor
Benign
1.9
L
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-2.2
N
REVEL
Uncertain
0.31
Sift
Uncertain
0.0060
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.81
MVP
0.34
MPC
1.0
ClinPred
0.72
D
GERP RS
4.1
Varity_R
0.44
gMVP
0.72

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: rs376868657; hg19: chr1-18691828; API