X-70146736-C-T

Variant names:

• chrX-70146736-C-T
• NM_001551.3:c.586C>T

Variant summary

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

The NM_001551.3(IGBP1):​c.586C>T​(p.His196Tyr) 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 benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: IGBP1 NM_001551.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10

Genes affected

IGBP1 (HGNC:5461): (immunoglobulin binding protein 1) The proliferation and differentiation of B cells is dependent upon a B-cell antigen receptor (BCR) complex. Binding of antigens to specific B-cell receptors results in a tyrosine phosphorylation reaction through the BCR complex and leads to multiple signal transduction pathways. [provided by RefSeq, Jul 2008]

ACMG classification

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
IGBP1	NM_001551.3	c.586C>T	p.His196Tyr	missense_variant	Exon 4 of 7	ENST00000356413.5	NP_001542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGBP1	ENST00000356413.5	c.586C>T	p.His196Tyr	missense_variant	Exon 4 of 7	1	NM_001551.3	ENSP00000348784.4
IGBP1	ENST00000342206.10	c.586C>T	p.His196Tyr	missense_variant	Exon 3 of 6	1		ENSP00000363661.5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.586C>T (p.H196Y) alteration is located in exon 4 (coding exon 3) of the IGBP1 gene. This alteration results from a C to T substitution at nucleotide position 586, causing the histidine (H) at amino acid position 196 to be replaced by a tyrosine (Y). 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	0.093
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Benign	0.77
DEOGEN2	Benign	0.017	T;T
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.64	.;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.71	N;N
REVEL	Benign	0.099
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0030	B;B
Vest4		0.55
MutPred		0.62		Loss of disorder (P = 0.1831);Loss of disorder (P = 0.1831);
MVP		0.51
MPC		0.51
ClinPred		0.14	T
GERP RS		4.3
Varity_R		0.12
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.32		Position offset: 9

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-69366586;