chr5-157732961-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The ENST00000231198.12(THG1L):​c.285G>A​(p.Glu95=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000603 in 1,614,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00060 ( 0 hom. )

Consequence

THG1L
ENST00000231198.12 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.17
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant 5-157732961-G-A is Benign according to our data. Variant chr5-157732961-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656002.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.17 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
THG1LNM_017872.5 linkuse as main transcriptc.285G>A p.Glu95= synonymous_variant 2/6 ENST00000231198.12 NP_060342.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
THG1LENST00000231198.12 linkuse as main transcriptc.285G>A p.Glu95= synonymous_variant 2/61 NM_017872.5 ENSP00000231198 P1
THG1LENST00000521655.1 linkuse as main transcriptc.285G>A p.Glu95= synonymous_variant, NMD_transcript_variant 2/62 ENSP00000428387

Frequencies

GnomAD3 genomes
AF:
0.000657
AC:
100
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00183
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000911
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000473
AC:
119
AN:
251488
Hom.:
0
AF XY:
0.000478
AC XY:
65
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000800
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000597
AC:
873
AN:
1461890
Hom.:
0
Cov.:
30
AF XY:
0.000576
AC XY:
419
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.000470
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.000739
Gnomad4 OTH exome
AF:
0.000348
GnomAD4 genome
AF:
0.000656
AC:
100
AN:
152330
Hom.:
0
Cov.:
32
AF XY:
0.000618
AC XY:
46
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.000192
Gnomad4 AMR
AF:
0.00183
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000911
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000640
Hom.:
0
Bravo
AF:
0.000506
EpiCase
AF:
0.000600
EpiControl
AF:
0.000533

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJun 01, 2024THG1L: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.47
CADD
Benign
7.8
DANN
Benign
0.89

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.

Other links and lift over

dbSNP: rs146250610; hg19: chr5-157159969; API