rs309204

Variant names:

• chr18-68676890-T-C
• rs309204
• NM_019022.5:c.*43A>G

Your query was ambiguous. Multiple possible variants found:

• chr18-68676890-T-C
• chr18-68676890-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_019022.5(TMX3):​c.*43A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,575,472 control chromosomes in the GnomAD database, including 1,658 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (851 hom., cov: 32)
  • Exomes 𝑓: 0.0075 (807 hom.)
• Consequence: TMX3 NM_019022.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.236
• Publications: 2 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 18-68676890-T-C is Benign according to our data. Variant chr18-68676890-T-C is described in ClinVar as Benign. ClinVar VariationId is 1251413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

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.*43A>G		3_prime_UTR	Exon 16 of 16	NP_061895.3
	TMX3	NM_001350514.2		c.*43A>G		3_prime_UTR	Exon 15 of 15	NP_001337443.1
	TMX3	NM_001350515.2		c.*43A>G		3_prime_UTR	Exon 15 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.*43A>G		3_prime_UTR	Exon 16 of 16	ENSP00000299608.2	Q96JJ7-1
	TMX3	ENST00000564631.5	TSL:1	n.*1092A>G		non_coding_transcript_exon	Exon 15 of 15	ENSP00000456587.1	H3BVI1
	TMX3	ENST00000564631.5	TSL:1	n.*1092A>G		3_prime_UTR	Exon 15 of 15	ENSP00000456587.1	H3BVI1

Frequencies

GnomAD3 genomes AF: 0.0602 AC: 9161 AN: 152130 Hom.: 844 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00176

Gnomad OTH AF: 0.0536

GnomAD2 exomes AF: 0.0184 AC: 4108 AN: 223866 AF XY: 0.0141

Gnomad AFR exome AF: 0.207

Gnomad AMR exome AF: 0.0180

Gnomad ASJ exome AF: 0.00818

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000501

Gnomad NFE exome AF: 0.00193

Gnomad OTH exome AF: 0.0130

GnomAD4 exome AF: 0.00751 AC: 10688 AN: 1423224 Hom.: 807 Cov.: 28 AF XY: 0.00678 AC XY: 4790 AN XY: 707002

African (AFR) AF: 0.216 AC: 6788 AN: 31440

American (AMR) AF: 0.0197 AC: 743 AN: 37642

Ashkenazi Jewish (ASJ) AF: 0.00803 AC: 194 AN: 24162

East Asian (EAS) AF: 0.00 AC: 0 AN: 39494

South Asian (SAS) AF: 0.000625 AC: 50 AN: 80024

European-Finnish (FIN) AF: 0.0000774 AC: 4 AN: 51696

Middle Eastern (MID) AF: 0.0223 AC: 123 AN: 5514

European-Non Finnish (NFE) AF: 0.00162 AC: 1769 AN: 1094550

Other (OTH) AF: 0.0173 AC: 1017 AN: 58702

GnomAD4 genome AF: 0.0603 AC: 9182 AN: 152248 Hom.: 851 Cov.: 32 AF XY: 0.0589 AC XY: 4387 AN XY: 74452

African (AFR) AF: 0.201 AC: 8348 AN: 41524

American (AMR) AF: 0.0366 AC: 560 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00720 AC: 25 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00176 AC: 120 AN: 68022

Other (OTH) AF: 0.0530 AC: 112 AN: 2112

Alfa AF: 0.0172 Hom.: 87

Bravo AF: 0.0699

Asia WGS AF: 0.0100 AC: 38 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		0.24
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: rs309204; hg19: chr18-66344127;