18-56614559-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004786.3(TXNL1):​c.600A>C​(p.Leu200Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>C	p.Leu200Leu	synonymous	Exon 6 of 8	NP_004777.1
	TXNL1	NR_024546.2		n.857A>C		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>C	p.Leu200Leu	synonymous	Exon 6 of 8	ENSP00000217515.5
	TXNL1	ENST00000586262.5	TSL:1	c.585A>C	p.Leu195Leu	synonymous	Exon 6 of 7	ENSP00000468165.1
	TXNL1	ENST00000590954.5	TSL:2	c.600A>C	p.Leu200Leu	synonymous	Exon 8 of 10	ENSP00000464918.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 599

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	10
DANN	Benign	0.66
PhyloP100		-1.2
PromoterAI		0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: -23

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs655539; hg19: chr18-54281790;