rs1554200371

Positions:

• chr6-81750332-T-C

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.692A>G​(p.Asp231Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: TENT5A NM_017633.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.02

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, 0.963
• PP5: Variant 6-81750332-T-C is Pathogenic according to our data. Variant chr6-81750332-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 523123.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.692A>G	p.Asp231Gly	missense_variant	3/3	ENST00000320172.11	NP_060103.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENT5A	ENST00000320172.11	c.692A>G	p.Asp231Gly	missense_variant	3/3	1	NM_017633.3	ENSP00000318298	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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	1.0
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	.;T;.
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	1.0	D;D;D
M_CAP	Benign	0.064	D
MetaRNN	Pathogenic	0.96	D;D;D
MetaSVM	Benign	-0.50	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Pathogenic	-6.7	D;D;D
REVEL	Pathogenic	0.77
Sift	Uncertain	0.0020	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.92
MutPred		0.90		.;Gain of sheet (P = 0.0827);.;
MVP		0.75
MPC		2.4
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.86
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.23		Position offset: 5

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554200371; hg19: chr6-82460049;