Genetic Variant TENT5A:p.Gly4Cys (chr6-81752132-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017633.3(TENT5A):c.10G>T(p.Gly4Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TENT5A
NM_017633.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43

Publications

5 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19414878).

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.10G>T	p.Gly4Cys	missense	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.10G>T	p.Gly4Cys	missense	Exon 2 of 3	ENSP00000318298.6
TENT5A	ENST00000369756.3	TSL:1	c.253G>T	p.Gly85Cys	missense	Exon 2 of 3	ENSP00000358771.3
TENT5A	ENST00000369754.7	TSL:1	c.67G>T	p.Gly23Cys	missense	Exon 2 of 3	ENSP00000358769.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1401120

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

692080

African (AFR)

AF:

0.00

AC:

AN:

31850

American (AMR)

AF:

0.00

AC:

AN:

37522

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24628

East Asian (EAS)

AF:

0.00

AC:

AN:

36844

South Asian (SAS)

AF:

0.00

AC:

AN:

79870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47964

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5564

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079074

Other (OTH)

AF:

0.00

AC:

AN:

57804

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0083

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.039

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.73

M_CAP

Benign

0.063

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

PhyloP100

1.4

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.21

REVEL

Benign

0.13

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

0.53

Vest4

0.55

MutPred

0.36

Loss of loop (P = 0.0603)

MVP

0.53

MPC

0.99

ClinPred

0.70

GERP RS

3.5

PromoterAI

-0.026

Neutral

(source)

Varity_R

0.23

gMVP

0.39

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over