NM_019022.5:c.843C>T

Variant names:

• chr18-68684195-G-A
• rs758562369
• NM_019022.5:c.843C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_019022.5(TMX3):​c.843C>T​(p.Phe281Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000687 in 1,456,610 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: TMX3 NM_019022.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73
• Publications: 0 publications found

Genes affected

TMX3 (HGNC:24718): (thioredoxin related transmembrane protein 3) This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The canonical protein encoded by this gene has an N-terminal ER-signal sequence, a catalytically active thioredoxin domain, one transmembrane domain and a C-terminal ER-retention sequence. This gene is expressed in many tissues but has its highest expression in heart and skeletal muscle. It is expressed in the retinal neuroepithelium and lens epithelium in the developing murine eye and haploinsufficiency of this gene in humans and zebrafish is associated with microphthalmia. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=2.73 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019022.5. 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
	TMX3	NM_019022.5	MANE Select	c.843C>T	p.Phe281Phe	synonymous	Exon 12 of 16	NP_061895.3
	TMX3	NM_001350514.2		c.762C>T	p.Phe254Phe	synonymous	Exon 11 of 15	NP_001337443.1
	TMX3	NM_001350515.2		c.420C>T	p.Phe140Phe	synonymous	Exon 11 of 15	NP_001337444.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMX3	ENST00000299608.7	TSL:1 MANE Select	c.843C>T	p.Phe281Phe	synonymous	Exon 12 of 16	ENSP00000299608.2	Q96JJ7-1
	TMX3	ENST00000564631.5	TSL:1	n.*527C>T		non_coding_transcript_exon	Exon 11 of 15	ENSP00000456587.1	H3BVI1
	TMX3	ENST00000564631.5	TSL:1	n.*527C>T		3_prime_UTR	Exon 11 of 15	ENSP00000456587.1	H3BVI1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000687 AC: 10 AN: 1456610 Hom.: 0 Cov.: 29 AF XY: 0.00000552 AC XY: 4 AN XY: 724810

African (AFR) AF: 0.00 AC: 0 AN: 33262

American (AMR) AF: 0.00 AC: 0 AN: 44330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.000228 AC: 9 AN: 39540

South Asian (SAS) AF: 0.00 AC: 0 AN: 85626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108582

Other (OTH) AF: 0.00 AC: 0 AN: 60156

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	8.5
DANN	Benign	0.80
PhyloP100		2.7

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

Other links and lift over

dbSNP: rs758562369; hg19: chr18-66351432; COSMIC: COSV55184071; COSMIC: COSV55184071;