dbSNP rs7222251: TSR1:c.*1374A>G (chr17-2322822-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_018128.5(TSR1):c.*1374A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 340,168 control chromosomes in the GnomAD database, including 13,081 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 0.29 ( 6288 hom., cov: 31)

Exomes 𝑓: 0.26 ( 6793 hom. )

Consequence

TSR1
NM_018128.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.206

Publications

7 publications found

Variant links:

Genes affected

TSR1 (HGNC:25542): (TSR1 ribosome maturation factor) Enables RNA binding activity. Predicted to be involved in endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) and maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be located in nucleolus. Predicted to be part of preribosome, small subunit precursor. [provided by Alliance of Genome Resources, Apr 2022]

TSR1 links:

SRR (HGNC:14398): (serine racemase) Enables several functions, including L-serine ammonia-lyase activity; PDZ domain binding activity; and anion binding activity. Involved in pyruvate biosynthetic process; response to lipopolysaccharide; and serine family amino acid metabolic process. Located in cytoplasm and neuronal cell body. [provided by Alliance of Genome Resources, Apr 2022]

SRR 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 (AMR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSR1	NM_018128.5 link	c.*1374A>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000301364.10	NP_060598.3	Q2NL82
SRR	NM_021947.3 link	c.595-314T>C		intron_variant	Intron 6 of 7	ENST00000344595.10	NP_068766.1	Q9GZT4Q3ZK31Q8N3F4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSR1	ENST00000301364.10 link	c.*1374A>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_018128.5	ENSP00000301364.4		Q2NL82
SRR	ENST00000344595.10 link	c.595-314T>C		intron_variant	Intron 6 of 7	1	NM_021947.3	ENSP00000339435.5		Q9GZT4

Frequencies

GnomAD3 genomes

AF:

0.287

AC:

43576

AN:

151688

Hom.:

6280

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.194

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.187

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.309

GnomAD4 exome

AF:

0.257

AC:

48394

AN:

188362

Hom.:

6793

Cov.:

AF XY:

0.249

AC XY:

25359

AN XY:

101964

show subpopulations

African (AFR)

AF:

0.324

AC:

1813

AN:

5602

American (AMR)

AF:

0.394

AC:

3211

AN:

8146

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

1276

AN:

4860

East Asian (EAS)

AF:

0.220

AC:

1874

AN:

8526

South Asian (SAS)

AF:

0.177

AC:

5835

AN:

32908

European-Finnish (FIN)

AF:

0.232

AC:

2066

AN:

8892

Middle Eastern (MID)

AF:

0.281

AC:

200

AN:

712

European-Non Finnish (NFE)

AF:

0.271

AC:

29541

AN:

109080

Other (OTH)

AF:

0.268

AC:

2578

AN:

9636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1670

3340

5011

6681

8351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

230

460

690

920

1150

<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:

0.287

AC:

43604

AN:

151806

Hom.:

6288

Cov.:

AF XY:

0.284

AC XY:

21081

AN XY:

74192

show subpopulations

African (AFR)

AF:

0.322

AC:

13317

AN:

41390

American (AMR)

AF:

0.359

AC:

5466

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

886

AN:

3464

East Asian (EAS)

AF:

0.227

AC:

1175

AN:

5166

South Asian (SAS)

AF:

0.187

AC:

902

AN:

4822

European-Finnish (FIN)

AF:

0.221

AC:

2327

AN:

10552

Middle Eastern (MID)

AF:

0.253

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.275

AC:

18633

AN:

67868

Other (OTH)

AF:

0.308

AC:

649

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1566

3131

4697

6262

7828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.288

Hom.:

800

Bravo

AF:

0.301

Asia WGS

AF:

0.232

AC:

808

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

3.1

(source)

DANN

Benign

0.55

PhyloP100

0.21

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