Variant 5-157731431-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BA1

The NM_017872.5(THG1L):c.-10C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,577,552 control chromosomes in the GnomAD database, including 19,725 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.11 ( 1338 hom., cov: 31)

Exomes 𝑓: 0.16 ( 18387 hom. )

Consequence

THG1L
NM_017872.5 5_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.84

Variant links:

Genes affected

THG1L (HGNC:26053): (tRNA-histidine guanylyltransferase 1 like) The protein encoded by this gene is a mitochondrial protein that is induced by high levels of glucose and is associated with diabetic nephropathy. The encoded protein appears to increase mitochondrial biogenesis, which could lead to renal fibrosis. Another function of this protein is that of a guanyltransferase, adding GMP to the 5' end of tRNA(His). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

THG1L links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 5-157731431-C-A is Benign according to our data. Variant chr5-157731431-C-A is described in ClinVar as [Benign]. Clinvar id is 3059739.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
THG1L	NM_017872.5 linkuse as main transcript	c.-10C>A	5_prime_UTR_variant	1/6	ENST00000231198.12	NP_060342.2
THG1L	NM_001317824.2 linkuse as main transcript	c.-311C>A	5_prime_UTR_variant	1/6		NP_001304753.1
THG1L	NM_001317825.2 linkuse as main transcript	c.-381C>A	5_prime_UTR_variant	1/6		NP_001304754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THG1L	ENST00000231198.12 linkuse as main transcript	c.-10C>A		5_prime_UTR_variant	1/6	1	NM_017872.5	ENSP00000231198	P1
THG1L	ENST00000521655.1 linkuse as main transcript	c.-10C>A		5_prime_UTR_variant, NMD_transcript_variant	1/6	2		ENSP00000428387

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17478

AN:

152006

Hom.:

1334

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0296

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.0952

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.124

GnomAD3 exomes

AF:

0.142

AC:

31641

AN:

222780

Hom.:

2690

AF XY:

0.150

AC XY:

17798

AN XY:

118758

show subpopulations

Gnomad AFR exome

AF:

0.0303

Gnomad AMR exome

AF:

0.0614

Gnomad ASJ exome

AF:

0.136

Gnomad EAS exome

AF:

0.196

Gnomad SAS exome

AF:

0.240

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.156

AC:

221931

AN:

1425428

Hom.:

18387

Cov.:

AF XY:

0.158

AC XY:

111220

AN XY:

705264

show subpopulations

Gnomad4 AFR exome

AF:

0.0269

Gnomad4 AMR exome

AF:

0.0649

Gnomad4 ASJ exome

AF:

0.132

Gnomad4 EAS exome

AF:

0.197

Gnomad4 SAS exome

AF:

0.224

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.159

Gnomad4 OTH exome

AF:

0.151

GnomAD4 genome

AF:

0.115

AC:

17484

AN:

152124

Hom.:

1338

Cov.:

AF XY:

0.115

AC XY:

8579

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0296

Gnomad4 AMR

AF:

0.0949

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.182

Gnomad4 SAS

AF:

0.234

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.126

Alfa

AF:

0.137

Hom.:

1813

Bravo

AF:

0.106

Asia WGS

AF:

0.214

AC:

741

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

THG1L-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 20, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over