5-134875365-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_024715.4(TXNDC15):c.103+836del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00683 in 456,282 control chromosomes in the GnomAD database, including 30 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0078 (29 hom.)
• Consequence: TXNDC15 NM_024715.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.06

Genes affected

TXNDC15 (HGNC:20652): (thioredoxin domain containing 15) 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. [provided by RefSeq, Apr 2017]

LOC124901071 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-134875365-GA-G is Benign according to our data. Variant chr5-134875365-GA-G is described in ClinVar as [Benign]. Clinvar id is 2655710.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00494 (752/152306) while in subpopulation SAS AF= 0.011 (53/4822). AF 95% confidence interval is 0.00863. There are 1 homozygotes in gnomad4. There are 345 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNDC15	NM_024715.4	c.103+836del		intron_variant		ENST00000358387.9
LOC124901071	XR_007058943.1	n.33del		non_coding_transcript_exon_variant	1/2
TXNDC15	NM_001350735.2	c.-102+883del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNDC15	ENST00000358387.9	c.103+836del		intron_variant		1	NM_024715.4	P1

Frequencies

GnomAD3 genomes AF: 0.00495 AC: 753 AN: 152188 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00811

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00669 AC: 859 AN: 128396 Hom.: 8 AF XY: 0.00720 AC XY: 506 AN XY: 70320

Gnomad AFR exome AF: 0.00246

Gnomad AMR exome AF: 0.00411

Gnomad ASJ exome AF: 0.000371

Gnomad EAS exome AF: 0.0000959

Gnomad SAS exome AF: 0.0126

Gnomad FIN exome AF: 0.00111

Gnomad NFE exome AF: 0.00894

Gnomad OTH exome AF: 0.00650

GnomAD4 exome AF: 0.00778 AC: 2366 AN: 303976 Hom.: 29 Cov.: 0 AF XY: 0.00837 AC XY: 1449 AN XY: 173086

Gnomad4 AFR exome AF: 0.00232

Gnomad4 AMR exome AF: 0.00418

Gnomad4 ASJ exome AF: 0.000649

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0129

Gnomad4 FIN exome AF: 0.00113

Gnomad4 NFE exome AF: 0.00827

Gnomad4 OTH exome AF: 0.00639

GnomAD4 genome AF: 0.00494 AC: 752 AN: 152306 Hom.: 1 Cov.: 32 AF XY: 0.00463 AC XY: 345 AN XY: 74478

Gnomad4 AFR AF: 0.00125

Gnomad4 AMR AF: 0.00464

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00812

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00168 Hom.: 2

Bravo AF: 0.00502

Asia WGS AF: 0.00318 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

TXNDC15: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

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: rs556892469; hg19: chr5-134211055; COSMIC: COSV64379613;