rs540421202

Variant names:

• chr7-45102398-C-A
• rs540421202
• NM_004749.4:c.1270G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-45102398-C-A
• chr7-45102398-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004749.4(TBRG4):​c.1270G>T​(p.Glu424*) variant causes a stop gained 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. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TBRG4 NM_004749.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.836
• Publications: 0 publications found

Genes affected

TBRG4 (HGNC:17443): (transforming growth factor beta regulator 4) Enables RNA binding activity. Involved in mitochondrial mRNA processing and regulation of mitochondrial mRNA stability. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004749.4. 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
	TBRG4	NM_004749.4	MANE Select	c.1270G>T	p.Glu424*	stop_gained	Exon 7 of 11	NP_004740.2
	TBRG4	NM_001261834.2		c.1303G>T	p.Glu435*	stop_gained	Exon 7 of 11	NP_001248763.1	B4DU42
	TBRG4	NM_030900.4		c.940G>T	p.Glu314*	stop_gained	Exon 5 of 9	NP_112162.1	Q969Z0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBRG4	ENST00000258770.8	TSL:1 MANE Select	c.1270G>T	p.Glu424*	stop_gained	Exon 7 of 11	ENSP00000258770.3	Q969Z0-1
	TBRG4	ENST00000361278.7	TSL:1	c.940G>T	p.Glu314*	stop_gained	Exon 5 of 9	ENSP00000354992.3	Q969Z0-2
	TBRG4	ENST00000495973.5	TSL:1	n.2559G>T		non_coding_transcript_exon	Exon 5 of 9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	38
DANN	Uncertain	0.99
Eigen	Uncertain	0.46
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.58	D
PhyloP100		0.84
Vest4		0.072
ClinPred		0.95	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=6/194	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.95		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.95		Position offset: 2

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

Other links and lift over

dbSNP: rs540421202; hg19: chr7-45141997;