12-98515429-C-T

Variant names:

• chr12-98515429-C-T
• rs117151045
• ENST00000548760.2:n.901G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000548760.2(TMPO-AS1):​n.901G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0706 in 178,054 control chromosomes in the GnomAD database, including 643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (533 hom., cov: 33)
  • Exomes 𝑓: 0.072 (110 hom.)
• Consequence: TMPO-AS1 ENST00000548760.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.597

Genes affected

TMPO-AS1 (HGNC:44158): (TMPO antisense RNA 1)

TMPO (HGNC:11875): (thymopoietin) Through alternative splicing, this gene encodes several distinct LEM domain containing protein isoforms. LEM domain proteins include inner nuclear membrane and intranuclear proteins, and are involved in a variety of cellular functions including gene expression, chromatin organization, and replication and cell cycle control. The encoded alpha isoform is broadly diffuse in the nucleus and contains a lamin binding domain, while the beta and gamma isoforms are localized to the nuclear membrane and contain an HDAC3 interaction domain. The distinct isoforms may compete with each other when acting to chaperone other proteins and regulate transcription. [provided by RefSeq, Aug 2019]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 12-98515429-C-T is Benign according to our data. Variant chr12-98515429-C-T is described in ClinVar as [Benign]. Clinvar id is 684009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPO	NM_001032283.3	c.-439C>T		upstream_gene_variant		ENST00000556029.6	NP_001027454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPO	ENST00000556029.6	c.-439C>T		upstream_gene_variant		1	NM_001032283.3	ENSP00000450627.1

Frequencies

GnomAD3 genomes AF: 0.0705 AC: 10712 AN: 152010 Hom.: 531 Cov.: 33

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.0596

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0964

Gnomad OTH AF: 0.0702

GnomAD4 exome AF: 0.0719 AC: 1865 AN: 25928 Hom.: 110 Cov.: 0 AF XY: 0.0767 AC XY: 1057 AN XY: 13786

Gnomad4 AFR exome AF: 0.0123

Gnomad4 AMR exome AF: 0.0421

Gnomad4 ASJ exome AF: 0.0564

Gnomad4 EAS exome AF: 0.00100

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.0635

Gnomad4 NFE exome AF: 0.0658

Gnomad4 OTH exome AF: 0.0678

GnomAD4 genome AF: 0.0704 AC: 10704 AN: 152126 Hom.: 533 Cov.: 33 AF XY: 0.0713 AC XY: 5302 AN XY: 74360

Gnomad4 AFR AF: 0.0179

Gnomad4 AMR AF: 0.0595

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0964

Gnomad4 OTH AF: 0.0695

Alfa AF: 0.0477 Hom.: 47

Bravo AF: 0.0628

Asia WGS AF: 0.0620 AC: 216 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs117151045; hg19: chr12-98909207;