rs113271462

Variant names:

• chr11-118339103-G-A
• rs113271462
• NM_000732.6:c.*59C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000732.6(CD3D):​c.*59C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,411,384 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (8 hom., cov: 31)
  • Exomes 𝑓: 0.00068 (6 hom.)
• Consequence: CD3D NM_000732.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.34
• Publications: 3 publications found

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]

CD3D Gene-Disease associations (from GenCC):

• immunodeficiency 19

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-118339103-G-A is Benign according to our data. Variant chr11-118339103-G-A is described in ClinVar as Benign. ClinVar VariationId is 302669.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0065 (990/152320) while in subpopulation AFR AF = 0.0227 (945/41554). AF 95% confidence interval is 0.0215. There are 8 homozygotes in GnomAd4. There are 494 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000732.6. 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
	CD3D	NM_000732.6	MANE Select	c.*59C>T		3_prime_UTR	Exon 5 of 5	NP_000723.1	P04234-1
	CD3D	NM_001040651.2		c.*59C>T		3_prime_UTR	Exon 4 of 4	NP_001035741.1	P04234-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD3D	ENST00000300692.9	TSL:1 MANE Select	c.*59C>T		3_prime_UTR	Exon 5 of 5	ENSP00000300692.4	P04234-1
	CD3D	ENST00000529594.5	TSL:1	c.*59C>T		3_prime_UTR	Exon 4 of 4	ENSP00000437335.1	E9PMT5
	CD3D	ENST00000392884.3	TSL:2	c.*59C>T		3_prime_UTR	Exon 4 of 4	ENSP00000376622.2	P04234-2

Frequencies

GnomAD3 genomes AF: 0.00643 AC: 979 AN: 152202 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00430

GnomAD4 exome AF: 0.000680 AC: 856 AN: 1259064 Hom.: 6 Cov.: 18 AF XY: 0.000581 AC XY: 370 AN XY: 636858

African (AFR) AF: 0.0240 AC: 706 AN: 29412

American (AMR) AF: 0.000855 AC: 38 AN: 44460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24900

East Asian (EAS) AF: 0.00 AC: 0 AN: 38816

South Asian (SAS) AF: 0.0000365 AC: 3 AN: 82152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.000186 AC: 1 AN: 5372

European-Non Finnish (NFE) AF: 0.0000291 AC: 27 AN: 927004

Other (OTH) AF: 0.00151 AC: 81 AN: 53650

GnomAD4 genome AF: 0.00650 AC: 990 AN: 152320 Hom.: 8 Cov.: 31 AF XY: 0.00663 AC XY: 494 AN XY: 74476

African (AFR) AF: 0.0227 AC: 945 AN: 41554

American (AMR) AF: 0.00183 AC: 28 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68030

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00322 Hom.: 1

Bravo AF: 0.00734

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency 19 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.74
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs113271462; hg19: chr11-118209818;