16-50153841-T-C

Variant names:

• chr16-50153841-T-C
• rs1334231262
• NM_001365324.3:c.220T>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001365324.3(TENT4B):​c.220T>C​(p.Ser74Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000178 in 1,124,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: TENT4B NM_001365324.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.114

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029086411).
• BP6: Variant 16-50153841-T-C is Benign according to our data. Variant chr16-50153841-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3176023.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENT4B	NM_001365324.3	c.220T>C	p.Ser74Pro	missense_variant	Exon 1 of 12	ENST00000561678.7	NP_001352253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENT4B	ENST00000561678.7	c.220T>C	p.Ser74Pro	missense_variant	Exon 1 of 12	5	NM_001365324.3	ENSP00000455837.3
TENT4B	ENST00000436909.8	c.175T>C	p.Ser59Pro	missense_variant	Exon 2 of 13	2		ENSP00000396995.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.000102 AC: 1 AN: 9786 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6650

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00164

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000178 AC: 2 AN: 1124234 Hom.: 0 Cov.: 32 AF XY: 0.00000185 AC XY: 1 AN XY: 541320

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 18, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.89
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.23	T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.1	T
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.049
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.22	T
Vest4		0.049
MutPred		0.14		Loss of phosphorylation at S59 (P = 0.0072);
MVP		0.10
MPC		1.5
ClinPred		0.079	T
GERP RS		2.0
gMVP		0.067

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: rs1334231262; hg19: chr16-50187752;