NM_000073.3:c.-50_-43delGCTGGCTG

Variant names:

• chr11-118344360-AGGCTGGCT-A
• rs60810919
• ENST00000292144.8:n.-50_-43delGCTGGCTG

Variant summary

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

The NM_000073.3(CD3G):​c.-50_-43delGCTGGCTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000323 in 1,237,622 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: CD3G NM_000073.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• 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 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
CD3G	NM_000073.3	c.-50_-43delGCTGGCTG		5_prime_UTR_variant	Exon 1 of 7	ENST00000532917.3	NP_000064.1
CD3G	NM_001440319.1	c.-50_-43delGCTGGCTG		5_prime_UTR_variant	Exon 1 of 7		NP_001427248.1
CD3G	XM_005271724.5	c.-50_-43delGCTGGCTG		5_prime_UTR_variant	Exon 1 of 4		XP_005271781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD3G	ENST00000532917.3	c.-50_-43delGCTGGCTG		5_prime_UTR_variant	Exon 1 of 7	1	NM_000073.3	ENSP00000431445.2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000323 AC: 4 AN: 1237622 Hom.: 0 AF XY: 0.00000485 AC XY: 3 AN XY: 617986

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28490

American (AMR) AF: 0.00 AC: 0 AN: 35502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24098

East Asian (EAS) AF: 0.00 AC: 0 AN: 34828

South Asian (SAS) AF: 0.00 AC: 0 AN: 75530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5174

European-Non Finnish (NFE) AF: 0.00000429 AC: 4 AN: 932624

Other (OTH) AF: 0.00 AC: 0 AN: 52494

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs60810919; hg19: chr11-118215075;