11-124625897-C-G

Variant names:

• chr11-124625897-C-G
• rs1413424167
• NM_032811.3:c.448C>G

Variant summary

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

The NM_032811.3(TBRG1):​c.448C>G​(p.Leu150Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,421,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: TBRG1 NM_032811.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.819

Genes affected

TBRG1 (HGNC:29551): (transforming growth factor beta regulator 1) Involved in several processes, including DNA replication; protein localization to nucleoplasm; and protein stabilization. Located in nucleoplasm. [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=0.046613693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBRG1	NM_032811.3	c.448C>G	p.Leu150Val	missense_variant	Exon 3 of 9	ENST00000441174.8	NP_116200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBRG1	ENST00000441174.8	c.448C>G	p.Leu150Val	missense_variant	Exon 3 of 9	1	NM_032811.3	ENSP00000409016.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000218 AC: 31 AN: 1421914 Hom.: 0 Cov.: 31 AF XY: 0.0000170 AC XY: 12 AN XY: 704164

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000283

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000286 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 19, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.448C>G (p.L150V) alteration is located in exon 3 (coding exon 3) of the TBRG1 gene. This alteration results from a C to G substitution at nucleotide position 448, causing the leucine (L) at amino acid position 150 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.14	N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.20
Sift	Benign	0.47	T
Sift4G	Benign	0.45	T
Polyphen		0.0020	B
Vest4		0.052
MutPred		0.13		Gain of methylation at K149 (P = 0.041);
MVP		0.77
MPC		0.016
ClinPred		0.18	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.031
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1413424167; hg19: chr11-124495793;