rs193922740

Variant names:

• chr1-167439354-T-A
• rs193922740
• ENST00000470379.2:c.-77A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-167439354-T-A
• chr1-167439354-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The ENST00000470379.2(CD247):​c.-77A>T variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CD247 ENST00000470379.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.867
• Publications: 3 publications found

Genes affected

CD247 (HGNC:1677): (CD247 molecule) The protein encoded by this gene is T-cell receptor zeta, which together with T-cell receptor alpha/beta and gamma/delta heterodimers, and with CD3-gamma, -delta and -epsilon, forms the T-cell receptor-CD3 complex. The zeta chain plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. Low expression of the antigen results in impaired immune response. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CD247 Gene-Disease associations (from GenCC):

• immunodeficiency 25

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-167439354-T-A is Pathogenic according to our data. Variant chr1-167439354-T-A is described in ClinVar as Pathogenic. ClinVar VariationId is 12751.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.22521862). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000470379.2. 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
	CD247	NM_198053.3	MANE Select	c.209A>T	p.Gln70Leu	missense	Exon 3 of 8	NP_932170.1
	CD247	NM_001378515.1		c.302A>T	p.Gln101Leu	missense	Exon 4 of 9	NP_001365444.1
	CD247	NM_001378516.1		c.302A>T	p.Gln101Leu	missense	Exon 4 of 9	NP_001365445.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD247	ENST00000470379.2	TSL:1	c.-77A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000514807.1
	CD247	ENST00000362089.10	TSL:1 MANE Select	c.209A>T	p.Gln70Leu	missense	Exon 3 of 8	ENSP00000354782.5
	CD247	ENST00000392122.4	TSL:1	c.209A>T	p.Gln70Leu	missense	Exon 3 of 8	ENSP00000375969.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Immunodeficiency 25 Pathogenic:1

May 04, 2006

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.87
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.039
Sift	Benign	0.12	T
Sift4G	Benign	0.28	T
Polyphen		0.0040	B
Vest4		0.42
MutPred		0.61		Loss of disorder (P = 0.0287)
MVP		0.48
MPC		0.16
ClinPred		0.76	D
GERP RS		0.16
Varity_R		0.40
gMVP		0.32
Mutation Taster		=12/88	disease causing (ClinVar)

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: rs193922740; hg19: chr1-167408591;