chr11-118344489-ACTAGGGGTCTGG-GGCTATCATTCTTCTTCAAGGTAAGGGCCTTC

Variant names:

• chr11-118344489-ACTAGGGGTCTGG-GGCTATCATTCTTCTTCAAGGTAAGGGCCTTC
• NM_000073.3:c.55+11_55+23delACTAGGGGTCTGGinsGGCTATCATTCTTCTTCAAGGTAAGGGCCTTC

Variant summary

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

The NM_000073.3(CD3G):​c.55+11_55+23delACTAGGGGTCTGGinsGGCTATCATTCTTCTTCAAGGTAAGGGCCTTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD3G NM_000073.3 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92
• Publications: 0 publications found

Genes affected

CD3G (HGNC:1675): (CD3 gamma subunit of T-cell receptor complex) The protein encoded by this gene is the CD3-gamma polypeptide, which together with CD3-epsilon, -delta and -zeta, and the T-cell receptor alpha/beta and gamma/delta heterodimers, forms the T-cell receptor-CD3 complex. This complex plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. The genes encoding the epsilon, gamma and delta polypeptides are located in the same cluster on chromosome 11. Defects in this gene are associated with T cell immunodeficiency. [provided by RefSeq, Jul 2008]

CD3G Gene-Disease associations (from GenCC):

• combined immunodeficiency due to CD3gamma deficiency

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD3G	NM_000073.3	c.55+11_55+23delACTAGGGGTCTGGinsGGCTATCATTCTTCTTCAAGGTAAGGGCCTTC		intron_variant	Intron 1 of 6	ENST00000532917.3	NP_000064.1
CD3G	NM_001440319.1	c.55+11_55+23delACTAGGGGTCTGGinsGGCTATCATTCTTCTTCAAGGTAAGGGCCTTC		intron_variant	Intron 1 of 6		NP_001427248.1
CD3G	XM_005271724.5	c.55+11_55+23delACTAGGGGTCTGGinsGGCTATCATTCTTCTTCAAGGTAAGGGCCTTC		intron_variant	Intron 1 of 3		XP_005271781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD3G	ENST00000532917.3	c.55+11_55+23delACTAGGGGTCTGGinsGGCTATCATTCTTCTTCAAGGTAAGGGCCTTC		intron_variant	Intron 1 of 6	1	NM_000073.3	ENSP00000431445.2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Combined immunodeficiency due to CD3gamma deficiency Uncertain:1

Feb 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change falls in intron 1 of the CD3G gene. It does not directly change the encoded amino acid sequence of the CD3G protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CD3G-related conditions. ClinVar contains an entry for this variant (Variation ID: 2027150). Experimental studies and prediction algorithms are not available or were not evaluated, and the effect of this variant on mRNA splicing is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

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

Other links and lift over

hg19: chr11-118215204;