1-52051740-A-G

Position:

• chr1-52051740-A-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNDC12	NM_015913.4	c.97+3260T>C		intron_variant		ENST00000371626.9	NP_056997.1
TXNDC12	NR_046405.1	n.1172+3260T>C		intron_variant
TXNDC12	NR_046406.1	n.1172+3260T>C		intron_variant
TXNDC12-AS1	NR_126385.1	n.49-44A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNDC12	ENST00000371626.9	c.97+3260T>C		intron_variant		1	NM_015913.4	ENSP00000360688.4
TXNDC12	ENST00000610127.2	c.97+3260T>C		intron_variant		2		ENSP00000476401.1
TXNDC12-AS1	ENST00000428794.1	n.49-44A>G		intron_variant		3
TXNDC12	ENST00000472624.5	n.97+3260T>C		intron_variant		5		ENSP00000477120.1

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

Gnomad4 AFR exome AF: 0.436

Gnomad4 AMR exome AF: 0.917

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.833

Gnomad4 SAS exome AF: 0.819

Gnomad4 FIN exome AF: 0.922

Gnomad4 NFE exome AF: 0.894

Gnomad4 OTH exome AF: 0.759

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

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.842

Gnomad4 ASJ AF: 0.903

Gnomad4 EAS AF: 0.835

Gnomad4 SAS AF: 0.816

Gnomad4 FIN AF: 0.924

Gnomad4 NFE AF: 0.888

Gnomad4 OTH AF: 0.792

Alfa AF: 0.830 Hom.: 16610

Bravo AF: 0.728

Asia WGS AF: 0.786 AC: 2736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs7529324; hg19: chr1-52517412; COSMIC: COSV57629030; COSMIC: COSV57629030;