22-23573289-C-T

Variant summary

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

The NM_020070.4(IGLL1):​c.619G>A​(p.Val207Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,870 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: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

IGLL1
NM_020070.4 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.74
Variant links:
Genes affected
IGLL1 (HGNC:5870): (immunoglobulin lambda like polypeptide 1) The preB cell receptor is found on the surface of proB and preB cells, where it is involved in transduction of signals for cellular proliferation, differentiation from the proB cell to the preB cell stage, allelic exclusion at the Ig heavy chain gene locus, and promotion of Ig light chain gene rearrangements. The preB cell receptor is composed of a membrane-bound Ig mu heavy chain in association with a heterodimeric surrogate light chain. This gene encodes one of the surrogate light chain subunits and is a member of the immunoglobulin gene superfamily. This gene does not undergo rearrangement. Mutations in this gene can result in B cell deficiency and agammaglobulinemia, an autosomal recessive disease in which few or no gamma globulins or antibodies are made. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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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=0.23742986).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IGLL1NM_020070.4 linkuse as main transcriptc.619G>A p.Val207Met missense_variant 3/3 ENST00000330377.3 NP_064455.1
IGLL1NM_001369906.1 linkuse as main transcriptc.622G>A p.Val208Met missense_variant 3/3 NP_001356835.1
IGLL1NM_152855.3 linkuse as main transcriptc.*248G>A 3_prime_UTR_variant 2/2 NP_690594.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IGLL1ENST00000330377.3 linkuse as main transcriptc.619G>A p.Val207Met missense_variant 3/31 NM_020070.4 ENSP00000329312 P1P15814-1
IGLL1ENST00000249053.3 linkuse as main transcriptc.*248G>A 3_prime_UTR_variant 2/21 ENSP00000249053 P15814-2
ENST00000458318.2 linkuse as main transcriptn.391-176C>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251438
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135900
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461870
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Agammaglobulinemia 2, autosomal recessive Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 01, 2022In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 947731). This variant has not been reported in the literature in individuals affected with IGLL1-related conditions. This variant is present in population databases (rs779159751, gnomAD 0.003%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 207 of the IGLL1 protein (p.Val207Met). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
13
DANN
Uncertain
0.99
DEOGEN2
Benign
0.39
T
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.74
FATHMM_MKL
Benign
0.030
N
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.0062
T
MetaRNN
Benign
0.24
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Pathogenic
3.0
M
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-2.5
N
REVEL
Benign
0.031
Sift
Uncertain
0.022
D
Sift4G
Benign
0.063
T
Polyphen
0.90
P
Vest4
0.11
MutPred
0.60
Loss of sheet (P = 0.0181);
MVP
0.14
MPC
0.31
ClinPred
0.62
D
GERP RS
1.4
Varity_R
0.22
gMVP
0.35

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: rs779159751; hg19: chr22-23915476; COSMIC: COSV99968663; COSMIC: COSV99968663; API