Variant 5-157731588-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017872.5(THG1L):c.148C>G(p.His50Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

THG1L
NM_017872.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24505213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THG1L	NM_017872.5 linkuse as main transcript	c.148C>G	p.His50Asp	missense_variant	1/6	ENST00000231198.12	NP_060342.2	Q9NWX6
THG1L	NM_001317825.2 linkuse as main transcript	c.-224C>G		5_prime_UTR_variant	1/6		NP_001304754.1	Q9NWX6Q9H8R6
THG1L	NM_001317824.2 linkuse as main transcript	c.-154C>G		5_prime_UTR_variant	1/6		NP_001304753.1	Q9NWX6B4E366

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THG1L	ENST00000231198.12 linkuse as main transcript	c.148C>G	p.His50Asp	missense_variant	1/6	1	NM_017872.5	ENSP00000231198.7		Q9NWX6
THG1L	ENST00000521655.1 linkuse as main transcript	n.148C>G		non_coding_transcript_exon_variant	1/6	2		ENSP00000428387.1		E5RIQ8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000806

AC:

AN:

248206

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134192

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000600

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:

0.00000137

AC:

AN:

1458512

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725452

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 20, 2024

The c.148C>G (p.H50D) alteration is located in exon 1 (coding exon 1) of the THG1L gene. This alteration results from a C to G substitution at nucleotide position 148, causing the histidine (H) at amino acid position 50 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.059

Eigen

Benign

-0.0097

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.0062

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.23

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.82

REVEL

Benign

0.15

Sift

Benign

0.15

Sift4G

Benign

0.18

Polyphen

0.0070

Vest4

0.40

MutPred

0.50

Loss of catalytic residue at C51 (P = 0.1669);

MVP

0.51

MPC

0.18

ClinPred

0.46

GERP RS

5.8

Varity_R

0.67

gMVP

0.48

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