Genetic Variant NM_001396518.1:c.*2445G>A (chr22-30973338-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_001396518.1(TUG1):c.*2445G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,998 control chromosomes in the GnomAD database, including 13,463 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 0.40 ( 13462 hom., cov: 32)

Exomes 𝑓: 0.75 ( 1 hom. )

Consequence

TUG1
NM_001396518.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0280

Publications

12 publications found

Variant links:

Genes affected

TUG1 (HGNC:26066): (taurine up-regulated 1) Predicted to act upstream of or within photoreceptor cell development and regulation of gene expression. Predicted to be active in nucleus. Biomarker of Huntington's disease. [provided by Alliance of Genome Resources, Apr 2022]

TUG1 links:

ENSG00000275307 (HGNC:):

ENSG00000275307 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=-0.74).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001396518.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TUG1	NM_001396518.1	MANE Select	c.*2445G>A	3_prime_UTR	Exon 2 of 3	NP_001383447.1
TUG1	NM_001398476.1		c.*2501G>A	3_prime_UTR	Exon 3 of 4	NP_001385405.1
TUG1	NM_001398477.1		c.*2445G>A	3_prime_UTR	Exon 2 of 3	NP_001385406.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TUG1	ENST00000644773.3	MANE Select	c.*2445G>A	3_prime_UTR	Exon 2 of 3	ENSP00000501406.2
TUG1	ENST00000519077.4	TSL:1	n.1075G>A	non_coding_transcript_exon	Exon 3 of 4
TUG1	ENST00000521091.6	TSL:1	n.953G>A	non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61365

AN:

151876

Hom.:

13444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.557

Gnomad AMI

AF:

0.295

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.659

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.326

Gnomad OTH

AF:

0.379

GnomAD4 exome

AF:

0.750

AC:

AN:

Hom.:

Cov.:

AF XY:

0.750

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.404

AC:

61423

AN:

151994

Hom.:

13462

Cov.:

AF XY:

0.403

AC XY:

29952

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.557

AC:

23068

AN:

41422

American (AMR)

AF:

0.363

AC:

5551

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

1141

AN:

3466

East Asian (EAS)

AF:

0.659

AC:

3412

AN:

5178

South Asian (SAS)

AF:

0.297

AC:

1429

AN:

4810

European-Finnish (FIN)

AF:

0.331

AC:

3495

AN:

10564

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.326

AC:

22177

AN:

67946

Other (OTH)

AF:

0.375

AC:

793

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1798

3596

5395

7193

8991

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

568

1136

1704

2272

2840

<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:

0.356

Hom.:

2430

Bravo

AF:

0.413

Asia WGS

AF:

0.465

AC:

1617

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.8

(source)

DANN

Benign

0.70

PhyloP100

0.028

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over