NM_006292.4:c.42+139A>C

Variant names:

• chr11-18526636-T-G
• rs1395319
• NM_006292.4:c.42+139A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006292.4(TSG101):​c.42+139A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 994,868 control chromosomes in the GnomAD database, including 71,359 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (10818 hom., cov: 33)
  • Exomes 𝑓: 0.37 (60541 hom.)
• Consequence: TSG101 NM_006292.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 7 publications found

Genes affected

TSG101 (HGNC:15971): (tumor susceptibility 101) The protein encoded by this gene belongs to a group of apparently inactive homologs of ubiquitin-conjugating enzymes. The gene product contains a coiled-coil domain that interacts with stathmin, a cytosolic phosphoprotein implicated in tumorigenesis. The protein may play a role in cell growth and differentiation and act as a negative growth regulator. In vitro steady-state expression of this tumor susceptibility gene appears to be important for maintenance of genomic stability and cell cycle regulation. Mutations and alternative splicing in this gene occur in high frequency in breast cancer and suggest that defects occur during breast cancer tumorigenesis and/or progression. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006292.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSG101	NM_006292.4	MANE Select	c.42+139A>C		intron	N/A	NP_006283.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSG101	ENST00000251968.4	TSL:1 MANE Select	c.42+139A>C		intron	N/A	ENSP00000251968.3
	TSG101	ENST00000438874.6	TSL:1	n.125+139A>C		intron	N/A
	TSG101	ENST00000536719.5	TSL:5	c.42+139A>C		intron	N/A	ENSP00000438471.1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55788 AN: 151824 Hom.: 10788 Cov.: 33

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.376

GnomAD4 exome AF: 0.367 AC: 309568 AN: 842926 Hom.: 60541 AF XY: 0.373 AC XY: 157745 AN XY: 423092

African (AFR) AF: 0.320 AC: 6166 AN: 19296

American (AMR) AF: 0.489 AC: 9270 AN: 18952

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 5792 AN: 16020

East Asian (EAS) AF: 0.703 AC: 21599 AN: 30720

South Asian (SAS) AF: 0.531 AC: 29233 AN: 55046

European-Finnish (FIN) AF: 0.436 AC: 13013 AN: 29818

Middle Eastern (MID) AF: 0.352 AC: 978 AN: 2776

European-Non Finnish (NFE) AF: 0.331 AC: 209031 AN: 631618

Other (OTH) AF: 0.375 AC: 14486 AN: 38680

GnomAD4 genome AF: 0.368 AC: 55857 AN: 151942 Hom.: 10818 Cov.: 33 AF XY: 0.376 AC XY: 27950 AN XY: 74270

African (AFR) AF: 0.330 AC: 13646 AN: 41410

American (AMR) AF: 0.409 AC: 6256 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1262 AN: 3470

East Asian (EAS) AF: 0.667 AC: 3440 AN: 5160

South Asian (SAS) AF: 0.549 AC: 2644 AN: 4820

European-Finnish (FIN) AF: 0.453 AC: 4786 AN: 10572

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22637 AN: 67912

Other (OTH) AF: 0.384 AC: 811 AN: 2110

Alfa AF: 0.350 Hom.: 1259

Bravo AF: 0.365

Asia WGS AF: 0.627 AC: 2180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.37
PhyloP100		0.082
PromoterAI		0.087	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs1395319; hg19: chr11-18548183;