NM_004786.3:c.600A>G

Variant names:

• chr18-56614559-T-C
• rs655539
• NM_004786.3:c.600A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

Genes affected

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004786.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNL1	NM_004786.3	MANE Select	c.600A>G	p.Leu200Leu	synonymous	Exon 6 of 8	NP_004777.1
	TXNL1	NR_024546.2		n.857A>G		non_coding_transcript_exon	Exon 7 of 9

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNL1	ENST00000217515.11	TSL:1 MANE Select	c.600A>G	p.Leu200Leu	synonymous	Exon 6 of 8	ENSP00000217515.5
	TXNL1	ENST00000586262.5	TSL:1	c.585A>G	p.Leu195Leu	synonymous	Exon 6 of 7	ENSP00000468165.1
	TXNL1	ENST00000590954.5	TSL:2	c.600A>G	p.Leu200Leu	synonymous	Exon 8 of 10	ENSP00000464918.1

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

GnomAD2 exomes AF: 0.0418 AC: 10480 AN: 250780 AF XY: 0.0425

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

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: 3 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

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

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: 1 AN: 5186

South Asian (SAS) AF: 0.0118 AC: 57 AN: 4826

European-Finnish (FIN) AF: 0.0699 AC: 742 AN: 10610

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0612 AC: 4163 AN: 68010

Other (OTH) AF: 0.0449 AC: 95 AN: 2116

Alfa AF: 0.0543 Hom.: 599

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	3.7
DANN	Benign	0.66
PhyloP100		-1.2
PromoterAI		-0.00060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs655539; hg19: chr18-54281790;