Genetic Variant NM_018128.5:c.2347G>A (chr17-2324264-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_018128.5(TSR1):c.2347G>A(p.Val783Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000793 in 1,550,276 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

TSR1
NM_018128.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.06

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08678299).

BS2

High AC in GnomAd4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018128.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSR1	NM_018128.5	MANE Select	c.2347G>A	p.Val783Ile	missense	Exon 15 of 15	NP_060598.3
SRR	NM_021947.3	MANE Select	c.*391C>T		3_prime_UTR	Exon 8 of 8	NP_068766.1	Q9GZT4
SRR	NM_001304803.1		c.*391C>T		3_prime_UTR	Exon 7 of 7	NP_001291732.1	Q3ZK31

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSR1	ENST00000301364.10	TSL:1 MANE Select	c.2347G>A	p.Val783Ile	missense	Exon 15 of 15	ENSP00000301364.4	Q2NL82
SRR	ENST00000344595.10	TSL:1 MANE Select	c.*391C>T		3_prime_UTR	Exon 8 of 8	ENSP00000339435.5	Q9GZT4
TSR1	ENST00000915544.1		c.2326G>A	p.Val776Ile	missense	Exon 15 of 15	ENSP00000585603.1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000113

AC:

AN:

194436

AF XY:

0.0000966

show subpopulations

Gnomad AFR exome

AF:

0.0000643

Gnomad AMR exome

AF:

0.000641

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000431

Gnomad OTH exome

AF:

0.000437

GnomAD4 exome

AF:

0.0000794

AC:

111

AN:

1398106

Hom.:

Cov.:

AF XY:

0.0000666

AC XY:

AN XY:

690534

show subpopulations

African (AFR)

AF:

0.0000323

AC:

AN:

31004

American (AMR)

AF:

0.000591

AC:

AN:

32128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21638

East Asian (EAS)

AF:

0.00

AC:

AN:

39364

South Asian (SAS)

AF:

0.0000135

AC:

AN:

73858

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51094

Middle Eastern (MID)

AF:

0.000732

AC:

AN:

5462

European-Non Finnish (NFE)

AF:

0.0000691

AC:

AN:

1085940

Other (OTH)

AF:

0.000191

AC:

AN:

57618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000789

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41438

American (AMR)

AF:

0.000131

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.000117

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000116

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

Eigen

Benign

0.083

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

M_CAP

Benign

0.0081

MetaRNN

Benign

0.087

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.6

PhyloP100

6.1

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.36

REVEL

Benign

0.11

Sift

Benign

0.16

Sift4G

Benign

0.14

Polyphen

0.43

Vest4

0.21

MVP

0.42

MPC

0.29

ClinPred

0.13

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.20

gMVP

0.31

Mutation Taster

=74/26

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over