X-136648396-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_000074.3(CD40LG):​c.148T>G​(p.Leu50Val) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 22)

Consequence

CD40LG
NM_000074.3 missense

Scores

9
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.309
Variant links:
Genes affected
CD40LG (HGNC:11935): (CD40 ligand) The protein encoded by this gene is expressed on the surface of T cells. It regulates B cell function by engaging CD40 on the B cell surface. A defect in this gene results in an inability to undergo immunoglobulin class switch and is associated with hyper-IgM syndrome. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1
In a topological_domain Extracellular (size 214) in uniprot entity CD40L_HUMAN there are 18 pathogenic changes around while only 0 benign (100%) in NM_000074.3
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29203644).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD40LGNM_000074.3 linkc.148T>G p.Leu50Val missense_variant Exon 1 of 5 ENST00000370629.7 NP_000065.1 P29965

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CD40LGENST00000370629.7 linkc.148T>G p.Leu50Val missense_variant Exon 1 of 5 1 NM_000074.3 ENSP00000359663.2 P29965

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.063
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.60
D;T
FATHMM_MKL
Benign
0.55
D
LIST_S2
Benign
0.82
T;T
M_CAP
Uncertain
0.15
D
MetaRNN
Benign
0.29
T;T
MetaSVM
Uncertain
-0.22
T
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-1.4
N;N
REVEL
Uncertain
0.41
Sift
Uncertain
0.0070
D;D
Sift4G
Uncertain
0.018
D;D
Polyphen
1.0
D;D
Vest4
0.25
MutPred
0.51
Loss of stability (P = 0.046);Loss of stability (P = 0.046);
MVP
0.84
MPC
1.2
ClinPred
0.83
D
GERP RS
1.2
Varity_R
0.18
gMVP
0.90

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: rs1126535; hg19: chrX-135730555; API