5-134887684-GC-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_024715.4(TXNDC15):c.104-10del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,554,846 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: TXNDC15 NM_024715.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.449

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 5-134887684-GC-G is Benign according to our data. Variant chr5-134887684-GC-G is described in ClinVar as [Benign]. Clinvar id is 2084183.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000407 (62/152188) while in subpopulation AMR AF= 0.0038 (58/15280). AF 95% confidence interval is 0.00301. There are 0 homozygotes in gnomad4. There are 34 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNDC15	NM_024715.4	c.104-10del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000358387.9
TXNDC15	NM_001350735.2	c.-101-10del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNDC15	ENST00000358387.9	c.104-10del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_024715.4	P1

Frequencies

GnomAD3 genomes AF: 0.000407 AC: 62 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000297 AC: 63 AN: 212350 Hom.: 0 AF XY: 0.000176 AC XY: 20 AN XY: 113698

Gnomad AFR exome AF: 0.0000637

Gnomad AMR exome AF: 0.00199

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000502

Gnomad OTH exome AF: 0.000397

GnomAD4 exome AF: 0.000103 AC: 145 AN: 1402658 Hom.: 0 Cov.: 30 AF XY: 0.000101 AC XY: 70 AN XY: 690132

Gnomad4 AFR exome AF: 0.0000627

Gnomad4 AMR exome AF: 0.00199

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000555

Gnomad4 OTH exome AF: 0.000173

GnomAD4 genome AF: 0.000407 AC: 62 AN: 152188 Hom.: 0 Cov.: 33 AF XY: 0.000457 AC XY: 34 AN XY: 74362

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00380

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000956

Bravo AF: 0.000487

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

Invitae

Nov 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs756023205; hg19: chr5-134223374;