chr1-52051740-A-G

Variant names:

• chr1-52051740-A-G
• rs7529324
• NM_015913.4:c.97+3260T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015913.4(TXNDC12):​c.97+3260T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 169,238 control chromosomes in the GnomAD database, including 53,299 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 0.75 (46183 hom., cov: 31)
  • Exomes 𝑓: 0.91 (7116 hom.)
• Consequence: TXNDC12 NM_015913.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609
• Publications: 3 publications found

Genes affected

TXNDC12 (HGNC:24626): (thioredoxin domain containing 12) This gene encodes a member of the thioredoxin superfamily. Members of this family are characterized by a conserved active motif called the thioredoxin fold that catalyzes disulfide bond formation and isomerization. This protein localizes to the endoplasmic reticulum and has a single atypical active motif. The encoded protein is mainly involved in catalyzing native disulfide bond formation and displays activity similar to protein-disulfide isomerases. This protein may play a role in defense against endoplasmic reticulum stress. Alternate splicing results in both coding and non-coding variants. [provided by RefSeq, Mar 2012]

TXNDC12-AS1 (HGNC:30008): (TXNDC12 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015913.4. 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
	TXNDC12	NM_015913.4	MANE Select	c.97+3260T>C		intron	N/A	NP_056997.1
	TXNDC12	NR_046405.1		n.1172+3260T>C		intron	N/A
	TXNDC12	NR_046406.1		n.1172+3260T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC12	ENST00000371626.9	TSL:1 MANE Select	c.97+3260T>C		intron	N/A	ENSP00000360688.4
	TXNDC12	ENST00000871920.1		c.97+3260T>C		intron	N/A	ENSP00000541979.1
	TXNDC12	ENST00000715260.1		c.97+3260T>C		intron	N/A	ENSP00000520430.1

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113944 AN: 152024 Hom.: 46176 Cov.: 31

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.903

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.924

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.793

GnomAD4 exome AF: 0.911 AC: 15572 AN: 17096 Hom.: 7116 Cov.: 0 AF XY: 0.912 AC XY: 7449 AN XY: 8166

African (AFR) AF: 0.436 AC: 34 AN: 78

American (AMR) AF: 0.917 AC: 11 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 3 AN: 4

East Asian (EAS) AF: 0.833 AC: 5 AN: 6

South Asian (SAS) AF: 0.819 AC: 77 AN: 94

European-Finnish (FIN) AF: 0.922 AC: 13548 AN: 14700

Middle Eastern (MID) AF: 0.872 AC: 1425 AN: 1634

European-Non Finnish (NFE) AF: 0.894 AC: 252 AN: 282

Other (OTH) AF: 0.759 AC: 217 AN: 286

GnomAD4 genome AF: 0.749 AC: 113970 AN: 152142 Hom.: 46183 Cov.: 31 AF XY: 0.755 AC XY: 56159 AN XY: 74370

African (AFR) AF: 0.403 AC: 16717 AN: 41456

American (AMR) AF: 0.842 AC: 12874 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.903 AC: 3135 AN: 3470

East Asian (EAS) AF: 0.835 AC: 4310 AN: 5160

South Asian (SAS) AF: 0.816 AC: 3937 AN: 4822

European-Finnish (FIN) AF: 0.924 AC: 9797 AN: 10604

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 60431 AN: 68026

Other (OTH) AF: 0.792 AC: 1670 AN: 2108

Alfa AF: 0.826 Hom.: 20482

Bravo AF: 0.728

Asia WGS AF: 0.786 AC: 2736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.62
PhyloP100		0.61
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: rs7529324; hg19: chr1-52517412; COSMIC: COSV57629030; COSMIC: COSV57629030;