rs655539

Positions:

• chr18-56614559-T-C
• chr18-56614559-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

Genes affected

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

TXNL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TXNL1	NM_004786.3	c.600A>G	p.Leu200Leu	synonymous_variant	6/8	ENST00000217515.11	NP_004777.1
TXNL1	XM_024451289.2	c.600A>G	p.Leu200Leu	synonymous_variant	6/9		XP_024307057.1
TXNL1	XM_024451290.2	c.600A>G	p.Leu200Leu	synonymous_variant	6/8		XP_024307058.1
TXNL1	NR_024546.2	n.857A>G		non_coding_transcript_exon_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNL1	ENST00000217515.11	c.600A>G	p.Leu200Leu	synonymous_variant	6/8	1	NM_004786.3	ENSP00000217515.5

Frequencies

GnomAD3 genomes AF: 0.0406 AC: 6180 AN: 152150 Hom.: 165 Cov.: 32

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

GnomAD3 exomes AF: 0.0418 AC: 10480 AN: 250780 Hom.: 301 AF XY: 0.0425 AC XY: 5762 AN XY: 135584

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 SAS exome AF: 0.0142

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.: 31 AF XY: 0.0516 AC XY: 37471 AN XY: 726880

Gnomad4 AFR exome AF: 0.00825

Gnomad4 AMR exome AF: 0.0278

Gnomad4 ASJ exome AF: 0.0473

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.0153

Gnomad4 FIN exome AF: 0.0673

Gnomad4 NFE exome AF: 0.0589

Gnomad4 OTH exome AF: 0.0435

GnomAD4 genome AF: 0.0406 AC: 6179 AN: 152266 Hom.: 166 Cov.: 32 AF XY: 0.0395 AC XY: 2942 AN XY: 74460

Gnomad4 AFR AF: 0.00982

Gnomad4 AMR AF: 0.0320

Gnomad4 ASJ AF: 0.0481

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.0699

Gnomad4 NFE AF: 0.0612

Gnomad4 OTH AF: 0.0449

Alfa AF: 0.0561 Hom.: 432

Bravo AF: 0.0368

Asia WGS AF: 0.00751 AC: 26 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
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs655539; hg19: chr18-54281790;