X-70146736-C-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

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10
Variant links:
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]

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ACMG classification

Classification made for transcript

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
IGBP1NM_001551.3 linkc.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
IGBP1ENST00000356413.5 linkc.586C>T p.His196Tyr missense_variant Exon 4 of 7 1 NM_001551.3 ENSP00000348784.4 P78318
IGBP1ENST00000342206.10 linkc.586C>T p.His196Tyr missense_variant Exon 3 of 6 1 ENSP00000363661.5 P78318

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
LINK: link

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; API