rs1187611948

Positions:

• chr6-81751762-T-C
• chr6-81751762-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_017633.3(TENT5A):​c.380A>G​(p.His127Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TENT5A NM_017633.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.92

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.973
• PP5: Variant 6-81751762-T-C is Pathogenic according to our data. Variant chr6-81751762-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 523122.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENT5A	NM_017633.3	c.380A>G	p.His127Arg	missense_variant	2/3	ENST00000320172.11	NP_060103.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENT5A	ENST00000320172.11	c.380A>G	p.His127Arg	missense_variant	2/3	1	NM_017633.3	ENSP00000318298.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000409 AC: 1 AN: 244574 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133674

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000552

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459972 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726322

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Osteogenesis imperfecta, type 18 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	.;T;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Benign	-0.75	T
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-6.5	D;D;D
REVEL	Pathogenic	0.76
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.038	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.95
MutPred		0.90		.;Gain of MoRF binding (P = 0.0137);.;
MVP		0.85
MPC		2.2
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.80
gMVP		0.99

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

LitVar

Other links and lift over

dbSNP: rs1187611948; hg19: chr6-82461479;