TGFBRAP1 p.Lys601Lys

Variant names:

• chr2-105273552-T-T
• NM_004257.6:c.

Your query was ambiguous. Multiple possible variants found:

• chr2-105273553--
• chr2-105273553-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004257.6(TGFBRAP1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TGFBRAP1 NM_004257.6 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304
• Publications: 0 publications found

Genes affected

TGFBRAP1 (HGNC:16836): (transforming growth factor beta receptor associated protein 1) This gene encodes a protein that binds to transforming growth factor-beta (TGF-beta) receptors and plays a role in TGF-beta signaling. The encoded protein acts as a chaprone in signaling downstream of TGF-beta. It is involved in signal-dependent association with SMAD4. The protein is also a component of mammalian CORVET, a multisubunit tethering protein complex that is involved in fusion of early endosomes. [provided by RefSeq, Jun 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004257.6. 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
	TGFBRAP1	NM_004257.6	MANE Select	c.		exon_region	Exon 9 of 12	NP_004248.2
	TGFBRAP1	NM_001142621.3		c.		exon_region	Exon 9 of 12	NP_001136093.1	Q8WUH2
	TGFBRAP1	NM_001328646.3		c.		exon_region	Exon 9 of 12	NP_001315575.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBRAP1	ENST00000393359.7	TSL:1 MANE Select	c.		exon_region	Exon 9 of 12	ENSP00000377027.2	Q8WUH2
	TGFBRAP1	ENST00000595531.5	TSL:1	c.		exon_region	Exon 8 of 11	ENSP00000471434.2	Q8WUH2
	TGFBRAP1	ENST00000911279.1		c.		exon_region	Exon 9 of 12	ENSP00000581338.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30

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: chr2-105890009;