chr18-56611057-C-T

Variant names:

• chr18-56611057-C-T
• NM_004786.3:c.776G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004786.3(TXNL1):​c.776G>A​(p.Arg259Lys) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TXNL1 NM_004786.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.21
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1405246).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNL1	NM_004786.3	MANE Select	c.776G>A	p.Arg259Lys	missense	Exon 7 of 8	NP_004777.1	O43396
	TXNL1	NR_024546.2		n.1033G>A		non_coding_transcript_exon	Exon 8 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNL1	ENST00000217515.11	TSL:1 MANE Select	c.776G>A	p.Arg259Lys	missense	Exon 7 of 8	ENSP00000217515.5	O43396
	TXNL1	ENST00000586262.5	TSL:1	c.761G>A	p.Arg254Lys	missense	Exon 7 of 7	ENSP00000468165.1	K7ER96
	TXNL1	ENST00000939694.1		c.824G>A	p.Arg275Lys	missense	Exon 8 of 9	ENSP00000609753.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.069
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.27	N
PhyloP100		3.2
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.082
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0090	B
Vest4		0.22
MutPred		0.60		Gain of sheet (P = 0.0125)
MVP		0.16
MPC		0.48
ClinPred		0.82	D
GERP RS		4.9
Varity_R		0.24
gMVP		0.50
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr18-54278288;