19-44613682-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001205280.2(IGSF23):ā€‹c.37C>Gā€‹(p.Pro13Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,550,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00045 ( 0 hom., cov: 32)
Exomes š‘“: 0.00019 ( 0 hom. )

Consequence

IGSF23
NM_001205280.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.801
Variant links:
Genes affected
IGSF23 (HGNC:40040): (immunoglobulin superfamily member 23) This gene encodes a protein that has one immunoglobulin (Ig) domain 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, Nov 2011]
CEACAM22P (HGNC:38029): (CEA cell adhesion molecule 22, pseudogene)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.010886043).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IGSF23NM_001205280.2 linkuse as main transcriptc.37C>G p.Pro13Ala missense_variant 1/5 ENST00000402988.6 NP_001192209.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IGSF23ENST00000402988.6 linkuse as main transcriptc.37C>G p.Pro13Ala missense_variant 1/53 NM_001205280.2 ENSP00000385592 P1
CEACAM22PENST00000455455.1 linkuse as main transcriptn.57+7083G>C intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.000447
AC:
68
AN:
152082
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00170
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000573
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000228
AC:
34
AN:
148912
Hom.:
0
AF XY:
0.000187
AC XY:
15
AN XY:
80140
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000407
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000927
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00149
Gnomad NFE exome
AF:
0.000128
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000193
AC:
270
AN:
1398030
Hom.:
0
Cov.:
32
AF XY:
0.000193
AC XY:
133
AN XY:
689502
show subpopulations
Gnomad4 AFR exome
AF:
0.0000633
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000280
Gnomad4 SAS exome
AF:
0.0000379
Gnomad4 FIN exome
AF:
0.00131
Gnomad4 NFE exome
AF:
0.000174
Gnomad4 OTH exome
AF:
0.000155
GnomAD4 genome
AF:
0.000447
AC:
68
AN:
152200
Hom.:
0
Cov.:
32
AF XY:
0.000511
AC XY:
38
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00170
Gnomad4 NFE
AF:
0.000573
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.000602
Hom.:
0
Bravo
AF:
0.000147
ExAC
AF:
0.0000697
AC:
2
Asia WGS
AF:
0.000866
AC:
3
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 GeneticsJan 09, 2024The c.37C>G (p.P13A) alteration is located in exon 1 (coding exon 1) of the IGSF23 gene. This alteration results from a C to G substitution at nucleotide position 37, causing the proline (P) at amino acid position 13 to be replaced by an alanine (A). 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
Benign
0.065
BayesDel_addAF
Benign
-0.64
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
0.089
DANN
Benign
0.36
DEOGEN2
Benign
0.0069
T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.077
N
LIST_S2
Benign
0.31
T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.011
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
0.20
N
REVEL
Benign
0.024
Sift
Benign
0.17
T
Sift4G
Benign
0.31
T
Vest4
0.10
MutPred
0.077
Loss of glycosylation at P13 (P = 0.0379);
MVP
0.055
ClinPred
0.026
T
GERP RS
-3.1
Varity_R
0.020
gMVP
0.19

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: rs755928659; hg19: chr19-45116992; API