rs1630312

chr1-117623069-C-Gchr1-117623069-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017709.4(TENT5C):c.201C>G(p.His67Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 1,614,004 control chromosomes in the GnomAD database, including 5,006 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.11 (1298 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3708 hom.)
• Consequence: TENT5C NM_017709.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.434

Genes affected

TENT5C (HGNC:24712): (terminal nucleotidyltransferase 5C) Enables RNA adenylyltransferase activity. Involved in mRNA stabilization. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017356277).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENT5C	NM_017709.4	c.201C>G	p.His67Gln	missense_variant	2/2	ENST00000369448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENT5C	ENST00000369448.4	c.201C>G	p.His67Gln	missense_variant	2/2	1	NM_017709.4	P1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16591 AN: 152006 Hom.: 1297 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.0821

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0634

Gnomad FIN AF: 0.0676

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0593

Gnomad OTH AF: 0.116

GnomAD3 exomes AF: 0.0774 AC: 19448 AN: 251420 Hom.: 977 AF XY: 0.0750 AC XY: 10188 AN XY: 135878

Gnomad AFR exome AF: 0.223

Gnomad AMR exome AF: 0.0691

Gnomad ASJ exome AF: 0.0841

Gnomad EAS exome AF: 0.119

Gnomad SAS exome AF: 0.0661

Gnomad FIN exome AF: 0.0630

Gnomad NFE exome AF: 0.0575

Gnomad OTH exome AF: 0.0771

GnomAD4 exome AF: 0.0639 AC: 93405 AN: 1461880 Hom.: 3708 Cov.: 65 AF XY: 0.0635 AC XY: 46170 AN XY: 727238

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.0730

Gnomad4 ASJ exome AF: 0.0805

Gnomad4 EAS exome AF: 0.0884

Gnomad4 SAS exome AF: 0.0686

Gnomad4 FIN exome AF: 0.0616

Gnomad4 NFE exome AF: 0.0561

Gnomad4 OTH exome AF: 0.0806

GnomAD4 genome AF: 0.109 AC: 16618 AN: 152124 Hom.: 1298 Cov.: 32 AF XY: 0.109 AC XY: 8118 AN XY: 74352

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.0819

Gnomad4 ASJ AF: 0.0873

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.0633

Gnomad4 FIN AF: 0.0676

Gnomad4 NFE AF: 0.0593

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0246 Hom.: 1458

TwinsUK AF: 0.0566 AC: 210

ALSPAC AF: 0.0527 AC: 203

ExAC AF: 0.0790 AC: 9598

EpiCase AF: 0.0642

EpiControl AF: 0.0663

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	18
Dann	Benign	0.95
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.087
Sift	Benign	0.18	T
Sift4G	Benign	0.12	T
Polyphen		0.0	B
Vest4		0.024
MutPred		0.14		Loss of methylation at R70 (P = 0.0447);
MPC		0.58
ClinPred		0.020	T
GERP RS		5.8
Varity_R		0.21
gMVP		0.18

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: rs1630312; hg19: chr1-118165691; COSMIC: COSV65616610;