22-23573314-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020070.4(IGLL1):​c.594C>G​(p.His198Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

IGLL1
NM_020070.4 missense

Scores

5
2
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.122
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.878

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IGLL1NM_020070.4 linkc.594C>G p.His198Gln missense_variant Exon 3 of 3 ENST00000330377.3 NP_064455.1 P15814-1
IGLL1NM_001369906.1 linkc.597C>G p.His199Gln missense_variant Exon 3 of 3 NP_001356835.1
IGLL1NM_152855.3 linkc.*223C>G 3_prime_UTR_variant Exon 2 of 2 NP_690594.1 P15814-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IGLL1ENST00000330377.3 linkc.594C>G p.His198Gln missense_variant Exon 3 of 3 1 NM_020070.4 ENSP00000329312.2 P15814-1
IGLL1ENST00000249053 linkc.*223C>G 3_prime_UTR_variant Exon 2 of 2 1 ENSP00000249053.3 P15814-2
ENSG00000224277ENST00000458318.2 linkn.391-151G>C intron_variant Intron 3 of 3 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.74
BayesDel_addAF
Benign
-0.092
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
10
DANN
Benign
0.87
DEOGEN2
Benign
0.38
T
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.99
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.0095
T
MetaRNN
Pathogenic
0.88
D
MetaSVM
Benign
-1.0
T
MutationAssessor
Pathogenic
3.6
H
PrimateAI
Uncertain
0.56
T
PROVEAN
Pathogenic
-7.0
D
REVEL
Benign
0.28
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0030
D
Polyphen
1.0
D
Vest4
0.69
MutPred
0.64
Loss of sheet (P = 0.0817);
MVP
0.16
MPC
0.35
ClinPred
0.97
D
GERP RS
-4.2
Varity_R
0.88
gMVP
0.76

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: rs1064418; hg19: chr22-23915501; API