16-50154194-C-G

Variant names:

• chr16-50154194-C-G
• NM_001365324.3:c.573C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365324.3(TENT4B):​c.573C>G​(p.Asp191Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TENT4B NM_001365324.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.97
• Publications: 0 publications found

Genes affected

TENT4B (HGNC:30758): (terminal nucleotidyltransferase 4B) Enables guanylyltransferase activity and polynucleotide adenylyltransferase activity. Involved in several processes, including RNA metabolic process; negative regulation of telomere maintenance via telomerase; and regulation of mRNA stability. Located in cytoplasm and nucleolus. Part of TRAMP complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.08606595).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365324.3. 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
	TENT4B	NM_001365324.3	MANE Select	c.573C>G	p.Asp191Glu	missense	Exon 1 of 12	NP_001352253.1	A0A7N4YH79
	TENT4B	NM_001040284.3		c.528C>G	p.Asp176Glu	missense	Exon 2 of 13	NP_001035374.2	Q8NDF8-5
	TENT4B	NM_001365323.2		c.513C>G	p.Asp171Glu	missense	Exon 2 of 13	NP_001352252.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENT4B	ENST00000561678.7	TSL:5 MANE Select	c.573C>G	p.Asp191Glu	missense	Exon 1 of 12	ENSP00000455837.3	A0A7N4YH79
	TENT4B	ENST00000436909.8	TSL:2	c.528C>G	p.Asp176Glu	missense	Exon 2 of 13	ENSP00000396995.3	Q8NDF8-5
	TENT4B	ENST00000562717.1	TSL:5	n.34C>G		non_coding_transcript_exon	Exon 1 of 13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.0
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.19	N
REVEL	Benign	0.087
Sift	Benign	0.31	T
Sift4G	Benign	1.0	T
Vest4		0.045
MVP		0.22
MPC		1.2
ClinPred		0.12	T
GERP RS		2.9
gMVP		0.28

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

hg19: chr16-50188105;