dbSNP rs655539: TXNL1:p.Leu200Leu (chr18-56614559-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004786.3(TXNL1):c.600A>G(p.Leu200Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 1,613,384 control chromosomes in the GnomAD database, including 2,465 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 0.041 ( 166 hom., cov: 32)

Exomes 𝑓: 0.052 ( 2299 hom. )

Consequence

TXNL1
NM_004786.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25

Publications

15 publications found

Variant links:

Genes affected

TXNL1 (HGNC:12436): (thioredoxin like 1) Enables disulfide oxidoreductase activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TXNL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP7

Synonymous conserved (PhyloP=-1.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNL1	NM_004786.3 link	c.600A>G	p.Leu200Leu	synonymous_variant	Exon 6 of 8	ENST00000217515.11	NP_004777.1	O43396V9HW51
TXNL1	XM_024451289.2 link	c.600A>G	p.Leu200Leu	synonymous_variant	Exon 6 of 9		XP_024307057.1
TXNL1	XM_024451290.2 link	c.600A>G	p.Leu200Leu	synonymous_variant	Exon 6 of 8		XP_024307058.1
TXNL1	NR_024546.2 link	n.857A>G		non_coding_transcript_exon_variant	Exon 7 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNL1	ENST00000217515.11 link	c.600A>G	p.Leu200Leu	synonymous_variant	Exon 6 of 8	1	NM_004786.3	ENSP00000217515.5		O43396

Frequencies

GnomAD3 genomes

AF:

0.0406

AC:

6180

AN:

152150

Hom.:

165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00985

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0321

Gnomad ASJ

AF:

0.0481

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0124

Gnomad FIN

AF:

0.0699

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0612

Gnomad OTH

AF:

0.0454

GnomAD2 exomes

AF:

0.0418

AC:

10480

AN:

250780

AF XY:

0.0425

show subpopulations

Gnomad AFR exome

AF:

0.0100

Gnomad AMR exome

AF:

0.0267

Gnomad ASJ exome

AF:

0.0471

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0685

Gnomad NFE exome

AF:

0.0593

Gnomad OTH exome

AF:

0.0474

GnomAD4 exome

AF:

0.0520

AC:

75945

AN:

1461118

Hom.:

2299

Cov.:

AF XY:

0.0516

AC XY:

37471

AN XY:

726880

show subpopulations

African (AFR)

AF:

0.00825

AC:

276

AN:

33458

American (AMR)

AF:

0.0278

AC:

1241

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.0473

AC:

1235

AN:

26114

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39646

South Asian (SAS)

AF:

0.0153

AC:

1315

AN:

86220

European-Finnish (FIN)

AF:

0.0673

AC:

3585

AN:

53278

Middle Eastern (MID)

AF:

0.0260

AC:

150

AN:

5762

European-Non Finnish (NFE)

AF:

0.0589

AC:

65514

AN:

1111592

Other (OTH)

AF:

0.0435

AC:

2626

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

3509

7019

10528

14038

17547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2288

4576

6864

9152

11440

<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:

0.0406

AC:

6179

AN:

152266

Hom.:

166

Cov.:

AF XY:

0.0395

AC XY:

2942

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00982

AC:

408

AN:

41562

American (AMR)

AF:

0.0320

AC:

489

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0481

AC:

167

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.0118

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0699

AC:

742

AN:

10610

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0612

AC:

4163

AN:

68010

Other (OTH)

AF:

0.0449

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

294

589

883

1178

1472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<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:

0.0543

Hom.:

599

Bravo

AF:

0.0368

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.0626

EpiControl

AF:

0.0628

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

3.7

(source)

DANN

Benign

0.66

PhyloP100

-1.2

PromoterAI

-0.00060

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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