Genetic Variant NM_152544.3:c.1131+529G>A (chr4-8453518-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_152544.3(TRMT44):c.1131+529G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 152,452 control chromosomes in the GnomAD database, including 16,979 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 0.46 ( 16945 hom., cov: 33)

Exomes 𝑓: 0.40 ( 34 hom. )

Consequence

TRMT44
NM_152544.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.516

Publications

3 publications found

Variant links:

Genes affected

TRMT44 (HGNC:26653): (tRNA methyltransferase 44 homolog) The protein encoded by this gene is a putative tRNA methyltransferase found in the cytoplasm. Defects in this gene may be a cause of partial epilepsy with pericentral spikes (PEPS), but that has not been proven definitively. [provided by RefSeq, May 2012]

TRMT44 links:

ENSG00000251186 (HGNC:58729):

ENSG00000251186 links:

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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=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT44	NM_152544.3 link	c.1131+529G>A		intron_variant	Intron 5 of 10	ENST00000389737.5	NP_689757.2	Q8IYL2-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRMT44	ENST00000389737.5 link	c.1131+529G>A	intron_variant	Intron 5 of 10	5	NM_152544.3	ENSP00000374387.4	Q8IYL2-1
TRMT44	ENST00000513449.6 link	c.408+529G>A	intron_variant	Intron 5 of 8	1		ENSP00000424643.2	Q8IYL2-2
ENSG00000251186	ENST00000515186.1 link	n.556C>T	non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70669

AN:

151922

Hom.:

16949

Cov.:

show subpopulations

Gnomad AFR

AF:

0.364

Gnomad AMI

AF:

0.461

Gnomad AMR

AF:

0.434

Gnomad ASJ

AF:

0.483

Gnomad EAS

AF:

0.528

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.523

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.460

GnomAD4 exome

AF:

0.398

AC:

164

AN:

412

Hom.:

Cov.:

AF XY:

0.412

AC XY:

AN XY:

238

show subpopulations

African (AFR)

AF:

0.375

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.167

AC:

AN:

South Asian (SAS)

AF:

0.750

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.400

AC:

140

AN:

350

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

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:

0.465

AC:

70683

AN:

152040

Hom.:

16945

Cov.:

AF XY:

0.469

AC XY:

34871

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.364

AC:

15072

AN:

41462

American (AMR)

AF:

0.434

AC:

6629

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.483

AC:

1675

AN:

3468

East Asian (EAS)

AF:

0.527

AC:

2721

AN:

5168

South Asian (SAS)

AF:

0.670

AC:

3229

AN:

4820

European-Finnish (FIN)

AF:

0.523

AC:

5525

AN:

10574

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.504

AC:

34276

AN:

67960

Other (OTH)

AF:

0.464

AC:

980

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1940

3881

5821

7762

9702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<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:

0.477

Hom.:

7589

Bravo

AF:

0.447

Asia WGS

AF:

0.579

AC:

2010

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.87

(source)

DANN

Benign

0.57

PhyloP100

-0.52

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