NM_017633.3:c.10G>C

Variant names:

• chr6-81752132-C-G
• rs11040
• NM_017633.3:c.10G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017633.3(TENT5A):​c.10G>C​(p.Gly4Arg) 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)
• Consequence: TENT5A NM_017633.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 5 publications found

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

ACMG classification

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=0.13062915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENT5A	NM_017633.3	c.10G>C	p.Gly4Arg	missense_variant	Exon 2 of 3	ENST00000320172.11	NP_060103.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENT5A	ENST00000320172.11	c.10G>C	p.Gly4Arg	missense_variant	Exon 2 of 3	1	NM_017633.3	ENSP00000318298.6
TENT5A	ENST00000369756.3	c.253G>C	p.Gly85Arg	missense_variant	Exon 2 of 3	1		ENSP00000358771.3
TENT5A	ENST00000369754.7	c.67G>C	p.Gly23Arg	missense_variant	Exon 2 of 3	1		ENSP00000358769.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0062	.;T;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		1.4
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.010	N;N;N
REVEL	Benign	0.046
Sift	Uncertain	0.0020	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.0	B;B;.
Vest4		0.41
MutPred		0.32		.;Loss of sheet (P = 0.0357);.;
MVP		0.40
MPC		1.1
ClinPred		0.66	D
GERP RS		3.5
PromoterAI		-0.047	Neutral
Varity_R		0.11
gMVP		0.25
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs11040; hg19: chr6-82461849;