11-124630425-TT-AC

Variant names:

• chr11-124630425-TT-AC
• NM_032811.3:c.776_777delTTinsAC
• TBRG1 p.Ile259Asn

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP2

The NM_032811.3(TBRG1):​c.776_777delTTinsAC​(p.Ile259Asn) variant causes a missense change. 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. I259T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBRG1 NM_032811.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.64
• 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 1 ACMG points.

• 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).

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.776_777delTTinsAC	p.Ile259Asn	missense	N/A	NP_116200.2	Q3YBR2-1
	TBRG1	NR_016021.2		n.859_860delTTinsAC		non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBRG1	ENST00000441174.8	TSL:1 MANE Select	c.776_777delTTinsAC	p.Ile259Asn	missense	N/A	ENSP00000409016.3	Q3YBR2-1
	TBRG1	ENST00000284290.8	TSL:1	n.*156_*157delTTinsAC		non_coding_transcript_exon	Exon 5 of 8	ENSP00000284290.4	F8W6N5
	TBRG1	ENST00000438907.3	TSL:1	n.382_383delTTinsAC		non_coding_transcript_exon	Exon 4 of 7

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.6

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: chr11-124500321;