Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.41

Publications

6 publications found

Variant links:

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]

TENT5A Gene-Disease associations (from GenCC):

osteogenesis imperfecta, type 18
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
osteogenesis imperfecta
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TENT5A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 402846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017633.3. 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
	TENT5A	NM_017633.3	MANE Select	c.117_131delCGGCGACTTCGGCGG	p.Gly40_Gly44del	disruptive_inframe_deletion	Exon 2 of 3	NP_060103.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TENT5A	ENST00000320172.11	TSL:1 MANE Select	c.117_131delCGGCGACTTCGGCGG	p.Gly40_Gly44del	disruptive_inframe_deletion	Exon 2 of 3	ENSP00000318298.6
TENT5A	ENST00000369756.3	TSL:1	c.360_374delCGGCGACTTCGGCGG	p.Gly121_Gly125del	disruptive_inframe_deletion	Exon 2 of 3	ENSP00000358771.3
TENT5A	ENST00000369754.7	TSL:1	c.174_188delCGGCGACTTCGGCGG	p.Gly59_Gly63del	disruptive_inframe_deletion	Exon 2 of 3	ENSP00000358769.3

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

32262

AN:

139508

Hom.:

3797

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.119

AC:

3026

AN:

25414

American (AMR)

AF:

0.242

AC:

9005

AN:

37192

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

7775

AN:

22922

East Asian (EAS)

AF:

0.121

AC:

4574

AN:

37828

South Asian (SAS)

AF:

0.242

AC:

17996

AN:

74432

European-Finnish (FIN)

AF:

0.259

AC:

11116

AN:

42960

Middle Eastern (MID)

AF:

0.233

AC:

955

AN:

4102

European-Non Finnish (NFE)

AF:

0.189

AC:

170983

AN:

904234

Other (OTH)

AF:

0.204

AC:

10491

AN:

51354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

7536

15072

22609

30145

37681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4430

8860

13290

17720

22150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.231

AC:

32254

AN:

139586

Hom.:

3795

Cov.:

AF XY:

0.234

AC XY:

15839

AN XY:

67668

show subpopulations

African (AFR)

AF:

0.141

AC:

5157

AN:

36568

American (AMR)

AF:

0.271

AC:

3858

AN:

14250

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

1279

AN:

3336

East Asian (EAS)

AF:

0.149

AC:

677

AN:

4544

South Asian (SAS)

AF:

0.302

AC:

1261

AN:

4178

European-Finnish (FIN)

AF:

0.307

AC:

2916

AN:

9510

Middle Eastern (MID)

AF:

0.269

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.253

AC:

16247

AN:

64118

Other (OTH)

AF:

0.262

AC:

507

AN:

1936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1120

2241

3361

4482

5602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

344

688

1032

1376

1720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.227

Hom.:

1118

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.4

Mutation Taster

=189/11

polymorphism (auto)

(source)

Splicing

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

Publications

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6-81752010-ACCGCCGAAGTCGCCGCCGCCGAAGTCGCCGCCGCCGAAGTCGCCG-ACCGCCGAAGTCGCCGCCGCCGAAGTCGCCG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over