chr6-81752010-A-ACCGCCGAAGTCGCCGCCGCCGAAGTCGCCGCCGCCGAAGTCGCCGCCGCCGAAGTCGCCG

Position:

• chr6-81752010-A-ACCGCCGAAGTCGCCGCCGCCGAAGTCGCCGCCGCCGAAGTCGCCGCCGCCGAAGTCGCCG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM4

The NM_017633.3(TENT5A):​c.72_131dupCGGCGACTTCGGCGGCGGCGACTTCGGCGGCGGCGACTTCGGCGGCGGCGACTTCGGCGG​(p.Gly44_Gly45insGlyAspPheGlyGlyGlyAspPheGlyGlyGlyAspPheGlyGlyGlyAspPheGlyGly) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (1 hom., cov: 0)
  • Exomes 𝑓: 0.000093 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TENT5A NM_017633.3 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 0.0420

Genes affected

TENT5A (HGNC:18345): (terminal nucleotidyltransferase 5A) Enables RNA binding activity. Predicted to be involved in mRNA stabilization. Predicted to act upstream of or within response to bacterium. Implicated in lung non-small cell carcinoma; osteoarthritis; and osteogenesis imperfecta type 18. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_017633.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENT5A	NM_017633.3	c.72_131dupCGGCGACTTCGGCGGCGGCGACTTCGGCGGCGGCGACTTCGGCGGCGGCGACTTCGGCGG	p.Gly44_Gly45insGlyAspPheGlyGlyGlyAspPheGlyGlyGlyAspPheGlyGlyGlyAspPheGlyGly	disruptive_inframe_insertion	2/3	ENST00000320172.11	NP_060103.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENT5A	ENST00000320172.11	c.72_131dupCGGCGACTTCGGCGGCGGCGACTTCGGCGGCGGCGACTTCGGCGGCGGCGACTTCGGCGG	p.Gly44_Gly45insGlyAspPheGlyGlyGlyAspPheGlyGlyGlyAspPheGlyGlyGlyAspPheGlyGly	disruptive_inframe_insertion	2/3	1	NM_017633.3	ENSP00000318298.6
TENT5A	ENST00000369756.3	c.315_374dupCGGCGACTTCGGCGGCGGCGACTTCGGCGGCGGCGACTTCGGCGGCGGCGACTTCGGCGG	p.Gly125_Gly126insGlyAspPheGlyGlyGlyAspPheGlyGlyGlyAspPheGlyGlyGlyAspPheGlyGly	disruptive_inframe_insertion	2/3	1		ENSP00000358771.3
TENT5A	ENST00000369754.7	c.129_188dupCGGCGACTTCGGCGGCGGCGACTTCGGCGGCGGCGACTTCGGCGGCGGCGACTTCGGCGG	p.Gly63_Gly64insGlyAspPheGlyGlyGlyAspPheGlyGlyGlyAspPheGlyGlyGlyAspPheGlyGly	disruptive_inframe_insertion	2/3	1		ENSP00000358769.3

Frequencies

GnomAD3 genomes AF: 0.000215 AC: 30 AN: 139636 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000478

Gnomad FIN AF: 0.000105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.000520

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000932 AC: 112 AN: 1201944 Hom.: 0 Cov.: 34 AF XY: 0.0000828 AC XY: 50 AN XY: 603562

Gnomad4 AFR exome AF: 0.000118

Gnomad4 AMR exome AF: 0.0000269

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000132

Gnomad4 SAS exome AF: 0.0000537

Gnomad4 FIN exome AF: 0.0000233

Gnomad4 NFE exome AF: 0.000100

Gnomad4 OTH exome AF: 0.000136

GnomAD4 genome AF: 0.000222 AC: 31 AN: 139714 Hom.: 1 Cov.: 0 AF XY: 0.000162 AC XY: 11 AN XY: 67722

Gnomad4 AFR AF: 0.000273

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000479

Gnomad4 FIN AF: 0.000105

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.000516

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

This variant, c.72_131dup, results in the insertion of 20 amino acid(s) of the FAM46A protein (p.Asp26_Gly45dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of osteogenesis imperfecta (Invitae). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

TENT5A-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 25, 2023

The TENT5A c.72_131dup60 variant is predicted to result in an in-frame duplication (p.Asp26_Gly45dup). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs754008809; hg19: chr6-82461727;