rs777329980

Variant names:

• chr6-81749896-C-G
• rs777329980
• NM_017633.3:c.1128G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-81749896-C-G
• chr6-81749896-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_017633.3(TENT5A):​c.1128G>C​(p.Gln376His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q376Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TENT5A NM_017633.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.86

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.883

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENT5A	NM_017633.3	c.1128G>C	p.Gln376His	missense_variant	Exon 3 of 3	ENST00000320172.11	NP_060103.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENT5A	ENST00000320172.11	c.1128G>C	p.Gln376His	missense_variant	Exon 3 of 3	1	NM_017633.3	ENSP00000318298.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	.;T;.
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Benign	-0.64	T
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-4.9	D;D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.88
MutPred		0.76		.;Gain of catalytic residue at L378 (P = 0.0632);.;
MVP		0.74
MPC		2.0
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.83
gMVP		0.88

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: rs777329980; hg19: chr6-82459613;