CD40LG p.Ser128Ser

Variant names:

• chrX-136656390-A-A
• ENST00000370629.7:c.

Your query was ambiguous. Multiple possible variants found:

• chrX-136656391--
• chrX-136656393-T-C
• chrX-136656391-AG-TC
• chrX-136656391-AGT-TCC
• chrX-136656391-AGT-TCA
• chrX-136656391-AGT-TCG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000074.3(CD40LG):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: CD40LG NM_000074.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67
• Publications: 0 publications found

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]

CD40LG Gene-Disease associations (from GenCC):

• hyper-IgM syndrome type 1

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000074.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD40LG	NM_000074.3	MANE Select	c.		intron	N/A	NP_000065.1	P29965

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD40LG	ENST00000370629.7	TSL:1 MANE Select	c.		exon_region	Exon 4 of 5	ENSP00000359663.2	P29965
	CD40LG	ENST00000370628.2	TSL:1	c.		intron	N/A	ENSP00000359662.2	Q3L8U2
	CD40LG	ENST00000695724.1		c.		exon_region	Exon 3 of 4	ENSP00000512122.1	A0A8Q3WKP2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-135738549;