chr1-52051740-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000371626.9(TXNDC12):​c.97+3260T>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TXNDC12 ENST00000371626.9 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371626.9. 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>G		intron	N/A	NP_056997.1
	TXNDC12	NR_046405.1		n.1172+3260T>G		intron	N/A
	TXNDC12	NR_046406.1		n.1172+3260T>G		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>G		intron	N/A	ENSP00000360688.4
	TXNDC12	ENST00000715260.1		c.97+3260T>G		intron	N/A	ENSP00000520430.1
	TXNDC12	ENST00000610127.2	TSL:2	c.97+3260T>G		intron	N/A	ENSP00000476401.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.63
PhyloP100		0.61

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;