7-45101573-C-G

Variant names:

• chr7-45101573-C-G
• NM_004749.4:c.1609G>C
• TBRG4 p.Val537Leu

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004749.4(TBRG4):​c.1609G>C​(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. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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: -0.0810
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034047604).

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.1609G>C	p.Val537Leu	missense	Exon 9 of 11	NP_004740.2
	TBRG4	NM_001261834.2		c.1642G>C	p.Val548Leu	missense	Exon 9 of 11	NP_001248763.1	B4DU42
	TBRG4	NM_030900.4		c.1279G>C	p.Val427Leu	missense	Exon 7 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.1609G>C	p.Val537Leu	missense	Exon 9 of 11	ENSP00000258770.3	Q969Z0-1
	TBRG4	ENST00000361278.7	TSL:1	c.1279G>C	p.Val427Leu	missense	Exon 7 of 9	ENSP00000354992.3	Q969Z0-2
	TBRG4	ENST00000495973.5	TSL:1	n.2898G>C		non_coding_transcript_exon	Exon 7 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
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.6
DANN	Benign	0.79
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.081
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.017
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Varity_R		0.020
gMVP		0.25
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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: chr7-45141172;