16-50154037-C-G

Variant names:

• chr16-50154037-C-G
• rs1183306874
• NM_001365324.3:c.416C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001365324.3(TENT4B):​c.416C>G​(p.Pro139Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,380,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P139L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TENT4B NM_001365324.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.890
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31201246).

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.416C>G	p.Pro139Arg	missense	Exon 1 of 12	NP_001352253.1	A0A7N4YH79
	TENT4B	NM_001040284.3		c.371C>G	p.Pro124Arg	missense	Exon 2 of 13	NP_001035374.2	Q8NDF8-5
	TENT4B	NM_001365323.2		c.356C>G	p.Pro119Arg	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.416C>G	p.Pro139Arg	missense	Exon 1 of 12	ENSP00000455837.3	A0A7N4YH79
	TENT4B	ENST00000436909.8	TSL:2	c.371C>G	p.Pro124Arg	missense	Exon 2 of 13	ENSP00000396995.3	Q8NDF8-5
	TENT4B	ENST00000562717.1	TSL:5	n.-124C>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1380464 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 681080

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31368

American (AMR) AF: 0.00 AC: 0 AN: 35278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25036

East Asian (EAS) AF: 0.00 AC: 0 AN: 35586

South Asian (SAS) AF: 0.00 AC: 0 AN: 78806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077526

Other (OTH) AF: 0.00 AC: 0 AN: 57760

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.89
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.16
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.48	T
Vest4		0.12
MutPred		0.81		Gain of MoRF binding (P = 0.0246)
MVP		0.34
MPC		1.3
ClinPred		0.14	T
GERP RS		0.71
gMVP		0.38

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: rs1183306874; hg19: chr16-50187948;