chr7-45101571-TAC-CAG

Variant names:

• chr7-45101571-TAC-CAG
• NM_004749.4:c.1609_1611delGTAinsCTG
• TBRG4 p.Val537Leu

Variant summary

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

The NM_004749.4(TBRG4):​c.1609_1611delGTAinsCTG​(p.Val537Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V537I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TBRG4 NM_004749.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.53
• 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 0 ACMG points.

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.1609_1611delGTAinsCTG	p.Val537Leu	missense	N/A	NP_004740.2
	TBRG4	NM_001261834.2		c.1642_1644delGTAinsCTG	p.Val548Leu	missense	N/A	NP_001248763.1	B4DU42
	TBRG4	NM_030900.4		c.1279_1281delGTAinsCTG	p.Val427Leu	missense	N/A	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.1609_1611delGTAinsCTG	p.Val537Leu	missense	N/A	ENSP00000258770.3	Q969Z0-1
	TBRG4	ENST00000361278.7	TSL:1	c.1279_1281delGTAinsCTG	p.Val427Leu	missense	N/A	ENSP00000354992.3	Q969Z0-2
	TBRG4	ENST00000495973.5	TSL:1	n.2898_2900delGTAinsCTG		non_coding_transcript_exon	Exon 7 of 9

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-45141170;