rs1143462

Variant names:

• chr7-45101926-A-C
• rs1143462
• NM_004749.4:c.1466T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-45101926-A-C
• chr7-45101926-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004749.4(TBRG4):​c.1466T>G​(p.Val489Gly) 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. 12/20 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. V489E) 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: 0.286

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066023946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBRG4	NM_004749.4	c.1466T>G	p.Val489Gly	missense_variant	Exon 8 of 11	ENST00000258770.8	NP_004740.2
TBRG4	NM_001261834.2	c.1499T>G	p.Val500Gly	missense_variant	Exon 8 of 11		NP_001248763.1
TBRG4	NM_030900.4	c.1136T>G	p.Val379Gly	missense_variant	Exon 6 of 9		NP_112162.1
TBRG4	NM_199122.3	c.1136T>G	p.Val379Gly	missense_variant	Exon 6 of 9		NP_954573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBRG4	ENST00000258770.8	c.1466T>G	p.Val489Gly	missense_variant	Exon 8 of 11	1	NM_004749.4	ENSP00000258770.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T;.;.;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.45	.;.;T;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.066	T;T;T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.3	N;D;D;N
REVEL	Benign	0.053
Sift	Uncertain	0.0010	D;T;T;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.20	B;D;D;B
Vest4		0.13
MutPred		0.41		Gain of relative solvent accessibility (P = 0.0166);.;.;Gain of relative solvent accessibility (P = 0.0166);
MVP		0.043
MPC		0.31
ClinPred		0.55	D
GERP RS		1.1
Varity_R		0.31
gMVP		0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs1143462; hg19: chr7-45141525;