NM_020070.4:c.594C>G

Variant names:

• chr22-23573314-G-C
• rs1064418
• NM_020070.4:c.594C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122

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]

ENSG00000224277 (HGNC:):

ACMG classification

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
IGLL1	NM_020070.4	c.594C>G	p.His198Gln	missense_variant	Exon 3 of 3	ENST00000330377.3	NP_064455.1
IGLL1	NM_001369906.1	c.597C>G	p.His199Gln	missense_variant	Exon 3 of 3		NP_001356835.1
IGLL1	NM_152855.3	c.*223C>G		3_prime_UTR_variant	Exon 2 of 2		NP_690594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGLL1	ENST00000330377.3	c.594C>G	p.His198Gln	missense_variant	Exon 3 of 3	1	NM_020070.4	ENSP00000329312.2
IGLL1	ENST00000249053	c.*223C>G		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000249053.3
ENSG00000224277	ENST00000458318.2	n.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

Other links and lift over

dbSNP: rs1064418; hg19: chr22-23915501;