chr16-50154042-C-T

Variant names:

• chr16-50154042-C-T
• rs771279160
• NM_001365324.3:c.421C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001365324.3(TENT4B):​c.421C>T​(p.Pro141Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,531,546 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: TENT4B NM_001365324.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.847
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040514708).
• BP6: Variant 16-50154042-C-T is Benign according to our data. Variant chr16-50154042-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3325383.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 6 AD gene.

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.421C>T	p.Pro141Ser	missense	Exon 1 of 12	NP_001352253.1	A0A7N4YH79
	TENT4B	NM_001040284.3		c.376C>T	p.Pro126Ser	missense	Exon 2 of 13	NP_001035374.2	Q8NDF8-5
	TENT4B	NM_001365323.2		c.361C>T	p.Pro121Ser	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.421C>T	p.Pro141Ser	missense	Exon 1 of 12	ENSP00000455837.3	A0A7N4YH79
	TENT4B	ENST00000436909.8	TSL:2	c.376C>T	p.Pro126Ser	missense	Exon 2 of 13	ENSP00000396995.3	Q8NDF8-5
	TENT4B	ENST00000562717.1	TSL:5	n.-119C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 152058 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000624 AC: 8 AN: 128282 AF XY: 0.0000427

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000299

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000253

GnomAD4 exome AF: 0.00000942 AC: 13 AN: 1379488 Hom.: 0 Cov.: 33 AF XY: 0.0000103 AC XY: 7 AN XY: 680596

African (AFR) AF: 0.0000319 AC: 1 AN: 31312

American (AMR) AF: 0.000285 AC: 10 AN: 35042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24986

East Asian (EAS) AF: 0.00 AC: 0 AN: 35526

South Asian (SAS) AF: 0.00 AC: 0 AN: 78660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1077166

Other (OTH) AF: 0.00 AC: 0 AN: 57724

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 152058 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74276

African (AFR) AF: 0.0000483 AC: 2 AN: 41424

American (AMR) AF: 0.000196 AC: 3 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.0000471 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.057
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.4
DANN	Benign	0.94
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.85
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.049
Sift	Benign	0.20	T
Sift4G	Benign	0.79	T
Vest4		0.038
MVP		0.19
MPC		1.2
ClinPred		0.023	T
GERP RS		0.73
gMVP		0.28
Mutation Taster		=90/10	polymorphism

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: rs771279160; hg19: chr16-50187953;