12-54974461-G-T

Variant names:

• chr12-54974461-G-T
• rs4758993
• NM_001136030.3:c.102C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001136030.3(TESPA1):​c.102C>A​(p.Ala34Ala) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TESPA1 NM_001136030.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 15 publications found

Genes affected

TESPA1 (HGNC:29109): (thymocyte expressed, positive selection associated 1) Predicted to enable phospholipase binding activity. Predicted to be involved in several processes, including COP9 signalosome assembly; positive regulation of T cell differentiation in thymus; and positive regulation of T cell receptor signaling pathway. Predicted to act upstream of or within TCR signalosome assembly. Part of COP9 signalosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-2.79 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136030.3. 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
	TESPA1	NM_001136030.3	MANE Select	c.102C>A	p.Ala34Ala	synonymous	Exon 2 of 11	NP_001129502.1	A2RU30-1
	TESPA1	NM_001098815.3		c.102C>A	p.Ala34Ala	synonymous	Exon 2 of 11	NP_001092285.1	A2RU30-1
	TESPA1	NM_001351149.2		c.102C>A	p.Ala34Ala	synonymous	Exon 3 of 12	NP_001338078.1	A2RU30-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TESPA1	ENST00000449076.6	TSL:2 MANE Select	c.102C>A	p.Ala34Ala	synonymous	Exon 2 of 11	ENSP00000400892.1	A2RU30-1
	TESPA1	ENST00000316577.12	TSL:1	c.102C>A	p.Ala34Ala	synonymous	Exon 2 of 11	ENSP00000312679.8	A2RU30-1
	TESPA1	ENST00000868657.1		c.102C>A	p.Ala34Ala	synonymous	Exon 3 of 12	ENSP00000538716.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.19
DANN	Benign	0.58
PhyloP100		-2.8

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: rs4758993; hg19: chr12-55368245;