6-81752010-ACCGCCGAAGTCGCCGCCGCCGAAGTCGCCGCCGCCGAAGTCGCCG-ACCGCCGAAGTCGCCGCCGCCGAAGTCGCCG

Position:

• chr6-81752010-ACCGCCGAAGTCGCCGCCGCCGAAGTCGCCGCCGCCGAAGTCGCCG-ACCGCCGAAGTCGCCGCCGCCGAAGTCGCCG

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BA1

The NM_017633.3(TENT5A):​c.117_131delCGGCGACTTCGGCGG​(p.Gly40_Gly44del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.2 in 1,340,024 control chromosomes in the GnomAD database, including 44,155 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (3795 hom., cov: 0)
  • Exomes 𝑓: 0.20 (40360 hom.)
• Consequence: TENT5A NM_017633.3 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 5.41

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 Benign. Variant got -14 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_017633.3.
• BP6: Variant 6-81752010-ACCGCCGAAGTCGCCG-A is Benign according to our data. Variant chr6-81752010-ACCGCCGAAGTCGCCG-A is described in ClinVar as [Benign]. Clinvar id is 402846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-81752010-ACCGCCGAAGTCGCCG-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENT5A	NM_017633.3	c.117_131delCGGCGACTTCGGCGG	p.Gly40_Gly44del	disruptive_inframe_deletion	2/3	ENST00000320172.11	NP_060103.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENT5A	ENST00000320172.11	c.117_131delCGGCGACTTCGGCGG	p.Gly40_Gly44del	disruptive_inframe_deletion	2/3	1	NM_017633.3	ENSP00000318298.6
TENT5A	ENST00000369756.3	c.360_374delCGGCGACTTCGGCGG	p.Gly121_Gly125del	disruptive_inframe_deletion	2/3	1		ENSP00000358771.3
TENT5A	ENST00000369754.7	c.174_188delCGGCGACTTCGGCGG	p.Gly59_Gly63del	disruptive_inframe_deletion	2/3	1		ENSP00000358769.3

Frequencies

GnomAD3 genomes AF: 0.231 AC: 32262 AN: 139508 Hom.: 3797 Cov.: 0

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.263

GnomAD4 exome AF: 0.197 AC: 235921 AN: 1200438 Hom.: 40360 AF XY: 0.198 AC XY: 119588 AN XY: 602938

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.339

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.242

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.231 AC: 32254 AN: 139586 Hom.: 3795 Cov.: 0 AF XY: 0.234 AC XY: 15839 AN XY: 67668

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.262

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 12, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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;