dbSNP rs1958281: TRMT5:c.*3521C>T (chr14-60971588-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020810.3(TRMT5):c.*3521C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 177,264 control chromosomes in the GnomAD database, including 76,318 homozygotes. 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: 𝑓 0.92 ( 64859 hom., cov: 33)

Exomes 𝑓: 0.95 ( 11459 hom. )

Consequence

TRMT5
NM_020810.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.475

Publications

4 publications found

Variant links:

Genes affected

TRMT5 (HGNC:23141): (tRNA methyltransferase 5) tRNAs contain as many as 13 or 14 nucleotides that are modified posttranscriptionally by enzymes that are highly specific for particular nucleotides in the tRNA structure. TRMT5 methylates the N1 position of guanosine-37 (G37) in selected tRNAs using S-adenosyl methionine (Brule et al., 2004 [PubMed 15248782]).[supplied by OMIM, Mar 2008]

TRMT5 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
combined oxidative phosphorylation defect type 26
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

TRMT5 links:

ENSG00000258892 (HGNC:):

ENSG00000258892 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.06).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TRMT5	NM_020810.3 link	c.*3521C>T	3_prime_UTR_variant	Exon 5 of 5	ENST00000261249.7	NP_065861.3	Q32P41
TRMT5	NM_001350253.1 link	c.*3521C>T	3_prime_UTR_variant	Exon 5 of 5		NP_001337182.1
TRMT5	NM_001350254.1 link	c.*3521C>T	3_prime_UTR_variant	Exon 5 of 5		NP_001337183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT5	ENST00000261249.7 link	c.*3521C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_020810.3	ENSP00000261249.6		Q32P41
ENSG00000258892	ENST00000553946.1 link	n.123-10920G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.919

AC:

139896

AN:

152180

Hom.:

64815

Cov.:

show subpopulations

Gnomad AFR

AF:

0.835

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.880

Gnomad ASJ

AF:

0.948

Gnomad EAS

AF:

0.788

Gnomad SAS

AF:

0.763

Gnomad FIN

AF:

0.990

Gnomad MID

AF:

0.934

Gnomad NFE

AF:

0.986

Gnomad OTH

AF:

0.923

GnomAD4 exome

AF:

0.955

AC:

23836

AN:

24966

Hom.:

11459

Cov.:

AF XY:

0.952

AC XY:

16284

AN XY:

17106

show subpopulations

African (AFR)

AF:

0.796

AC:

242

AN:

304

American (AMR)

AF:

0.842

AC:

527

AN:

626

Ashkenazi Jewish (ASJ)

AF:

0.952

AC:

474

AN:

498

East Asian (EAS)

AF:

0.707

AC:

472

AN:

668

South Asian (SAS)

AF:

0.783

AC:

1458

AN:

1862

European-Finnish (FIN)

AF:

0.991

AC:

947

AN:

956

Middle Eastern (MID)

AF:

0.942

AC:

AN:

104

European-Non Finnish (NFE)

AF:

0.986

AC:

18517

AN:

18782

Other (OTH)

AF:

0.944

AC:

1101

AN:

1166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

121

162

202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.919

AC:

139999

AN:

152298

Hom.:

64859

Cov.:

AF XY:

0.915

AC XY:

68158

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.835

AC:

34701

AN:

41534

American (AMR)

AF:

0.880

AC:

13468

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.948

AC:

3291

AN:

3472

East Asian (EAS)

AF:

0.788

AC:

4079

AN:

5176

South Asian (SAS)

AF:

0.765

AC:

3695

AN:

4828

European-Finnish (FIN)

AF:

0.990

AC:

10512

AN:

10622

Middle Eastern (MID)

AF:

0.939

AC:

276

AN:

294

European-Non Finnish (NFE)

AF:

0.986

AC:

67123

AN:

68042

Other (OTH)

AF:

0.919

AC:

1942

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

518

1036

1553

2071

2589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.952

Hom.:

27058

Bravo

AF:

0.910

Asia WGS

AF:

0.771

AC:

2683

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.10

(source)

DANN

Benign

0.47

PhyloP100

0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over