6-81752132-C-T

Variant names:

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

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>A​(p.Gly4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,401,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 7.1e-7 (0 hom.)
• 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=0.11370823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENT5A	NM_017633.3	c.10G>A	p.Gly4Ser	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>A	p.Gly4Ser	missense_variant	Exon 2 of 3	1	NM_017633.3	ENSP00000318298.6
TENT5A	ENST00000369756.3	c.253G>A	p.Gly85Ser	missense_variant	Exon 2 of 3	1		ENSP00000358771.3
TENT5A	ENST00000369754.7	c.67G>A	p.Gly23Ser	missense_variant	Exon 2 of 3	1		ENSP00000358769.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1401120 Hom.: 0 Cov.: 41 AF XY: 0.00000144 AC XY: 1 AN XY: 692080

African (AFR) AF: 0.00 AC: 0 AN: 31850

American (AMR) AF: 0.00 AC: 0 AN: 37522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24628

East Asian (EAS) AF: 0.00 AC: 0 AN: 36844

South Asian (SAS) AF: 0.00 AC: 0 AN: 79870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5564

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079074

Other (OTH) AF: 0.0000173 AC: 1 AN: 57804

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0058	.;T;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		1.4
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	0.29	N;N;N
REVEL	Benign	0.050
Sift	Benign	0.044	D;D;D
Sift4G	Pathogenic	0.0	D;D;T
Polyphen		0.0	B;B;.
Vest4		0.24
MutPred		0.32		.;Loss of sheet (P = 0.0126);.;
MVP		0.49
MPC		0.93
ClinPred		0.59	D
GERP RS		3.5
PromoterAI		-0.028	Neutral
Varity_R		0.049
gMVP		0.21
Mutation Taster		=93/7	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;