chr11-124624938-C-T

Variant names:

• chr11-124624938-C-T
• NM_032811.3:c.158C>T

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PP2 PP3_Moderate

The NM_032811.3(TBRG1):​c.158C>T​(p.Ala53Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBRG1 NM_032811.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.66
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.8118 (below the threshold of 3.09). Trascript score misZ: 0.037837 (below the threshold of 3.09).
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.84

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032811.3. 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
	TBRG1	NM_032811.3	MANE Select	c.158C>T	p.Ala53Val	missense	Exon 2 of 9	NP_116200.2	Q3YBR2-1
	TBRG1	NR_016021.2		n.378C>T		non_coding_transcript_exon	Exon 2 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBRG1	ENST00000441174.8	TSL:1 MANE Select	c.158C>T	p.Ala53Val	missense	Exon 2 of 9	ENSP00000409016.3	Q3YBR2-1
	TBRG1	ENST00000284290.8	TSL:1	n.158C>T		non_coding_transcript_exon	Exon 2 of 8	ENSP00000284290.4	F8W6N5
	TBRG1	ENST00000529543.5	TSL:1	n.158C>T		non_coding_transcript_exon	Exon 2 of 7	ENSP00000436599.1	E9PI10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1386202 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 684160

African (AFR) AF: 0.00 AC: 0 AN: 31252

American (AMR) AF: 0.00 AC: 0 AN: 35220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25056

East Asian (EAS) AF: 0.00 AC: 0 AN: 35604

South Asian (SAS) AF: 0.00 AC: 0 AN: 77730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1068598

Other (OTH) AF: 0.00 AC: 0 AN: 57646

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.36
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.7
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.8	D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.75
MutPred		0.44		Loss of disorder (P = 0.0611)
MVP		0.97
MPC		0.057
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.57
gMVP		0.48
Mutation Taster		=7/93	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr11-124494834;