rs483352927

Variant names:

• chr11-118349740-CAGGAAACCACTTGGTTA-C
• rs483352927
• NM_000073.3:c.81_97delAAACCACTTGGTTAAGG

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PVS1_Strong PP5

The NM_000073.3(CD3G):​c.81_97delAAACCACTTGGTTAAGG​(p.Asn28fs) variant causes a frameshift, splice region 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 DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CD3G NM_000073.3 frameshift, splice_region
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.97
• Publications: 2 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 5 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 10 pathogenic variants in the truncated region.
• PP5: Variant 11-118349740-CAGGAAACCACTTGGTTA-C is Pathogenic according to our data. Variant chr11-118349740-CAGGAAACCACTTGGTTA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 12754.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000073.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD3G	NM_000073.3	MANE Select	c.81_97delAAACCACTTGGTTAAGG	p.Asn28fs	frameshift splice_region	Exon 3 of 7	NP_000064.1
	CD3G	NM_001440319.1		c.81_97delAAACCACTTGGTTAAGG	p.Asn28fs	frameshift splice_region	Exon 3 of 7	NP_001427248.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD3G	ENST00000532917.3	TSL:1 MANE Select	c.81_97delAAACCACTTGGTTAAGG	p.Asn28fs	frameshift splice_region	Exon 3 of 7	ENSP00000431445.2
	CD3G	ENST00000528540.5	TSL:1	c.-84-16_-84delAAACCACTTGGTTAAGG		splice_region	Exon 3 of 3	ENSP00000498162.1
	CD3G	ENST00000292144.8	TSL:1	n.*138_*154delAAACCACTTGGTTAAGG		splice_region non_coding_transcript_exon	Exon 4 of 8	ENSP00000292144.4

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Combined immunodeficiency due to CD3gamma deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0
Mutation Taster		=64/136	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs483352927; hg19: chr11-118220455;