NM_000732.6:c.505C>G

Variant names:

• chr11-118339173-G-C
• rs367800432
• NM_000732.6:c.505C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000732.6(CD3D):​c.505C>G​(p.Arg169Gly) 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. 12/21 in silico tools predict 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: 31)
• Consequence: CD3D NM_000732.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

Genes affected

CD3D (HGNC:1673): (CD3 delta subunit of T-cell receptor complex) The protein encoded by this gene is part of the T-cell receptor/CD3 complex (TCR/CD3 complex) and is involved in T-cell development and signal transduction. The encoded membrane protein represents the delta subunit of the CD3 complex, and along with four other CD3 subunits, binds either TCR alpha/beta or TCR gamma/delta to form the TCR/CD3 complex on the surface of T-cells. Defects in this gene are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-positive (SCIDBNK). Two transcript variants encoding different isoforms have been found for this gene. Other variants may also exist, but the full-length natures of their transcripts has yet to be defined. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3442261).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD3D	NM_000732.6	c.505C>G	p.Arg169Gly	missense_variant	Exon 5 of 5	ENST00000300692.9	NP_000723.1
CD3D	NM_001040651.2	c.373C>G	p.Arg125Gly	missense_variant	Exon 4 of 4		NP_001035741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD3D	ENST00000300692.9	c.505C>G	p.Arg169Gly	missense_variant	Exon 5 of 5	1	NM_000732.6	ENSP00000300692.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.91	D;.;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.6	M;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-6.0	D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.33
MutPred		0.60		Loss of MoRF binding (P = 6e-04);.;.;
MVP		0.85
MPC		0.74
ClinPred		0.98	D
GERP RS		1.0
Varity_R		0.28
gMVP		0.57

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

Other links and lift over

dbSNP: rs367800432; hg19: chr11-118209888;