rs1768990052

Variant names:

• chr6-81749713-A-C
• rs1768990052
• NM_017633.3:c.1311T>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_017633.3(TENT5A):​c.1311T>G​(p.Thr437Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TENT5A NM_017633.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.55
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 6-81749713-A-C is Benign according to our data. Variant chr6-81749713-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2706692.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.55 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENT5A	NM_017633.3	MANE Select	c.1311T>G	p.Thr437Thr	synonymous	Exon 3 of 3	NP_060103.2	Q96IP4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENT5A	ENST00000320172.11	TSL:1 MANE Select	c.1311T>G	p.Thr437Thr	synonymous	Exon 3 of 3	ENSP00000318298.6	Q96IP4-1
	TENT5A	ENST00000369756.3	TSL:1	c.1554T>G	p.Thr518Thr	synonymous	Exon 3 of 3	ENSP00000358771.3	Q5TF85
	TENT5A	ENST00000369754.7	TSL:1	c.1368T>G	p.Thr456Thr	synonymous	Exon 3 of 3	ENSP00000358769.3	Q96IP4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460586 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 726378

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110984

Other (OTH) AF: 0.00 AC: 0 AN: 60342

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	10
DANN	Benign	0.73
PhyloP100		2.6

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: rs1768990052; hg19: chr6-82459430;