5-134887903-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024715.4(TXNDC15):c.312A>G(p.Lys104=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,614,102 control chromosomes in the GnomAD database, including 17,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1341 hom., cov: 33)
  • Exomes 𝑓: 0.14 (16374 hom.)
• Consequence: TXNDC15 NM_024715.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.543

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 5-134887903-A-G is Benign according to our data. Variant chr5-134887903-A-G is described in ClinVar as [Benign]. Clinvar id is 1559526.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNDC15	NM_024715.4	c.312A>G	p.Lys104=	synonymous_variant	2/5	ENST00000358387.9
TXNDC15	NM_001350735.2	c.108A>G	p.Lys36=	synonymous_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNDC15	ENST00000358387.9	c.312A>G	p.Lys104=	synonymous_variant	2/5	1	NM_024715.4	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18581 AN: 152112 Hom.: 1336 Cov.: 33

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.112

GnomAD3 exomes AF: 0.151 AC: 37881 AN: 251418 Hom.: 3167 AF XY: 0.152 AC XY: 20696 AN XY: 135884

Gnomad AFR exome AF: 0.0535

Gnomad AMR exome AF: 0.168

Gnomad ASJ exome AF: 0.0790

Gnomad EAS exome AF: 0.244

Gnomad SAS exome AF: 0.193

Gnomad FIN exome AF: 0.204

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.143 AC: 208423 AN: 1461872 Hom.: 16374 Cov.: 32 AF XY: 0.144 AC XY: 104528 AN XY: 727236

Gnomad4 AFR exome AF: 0.0507

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.0797

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.206

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.122 AC: 18599 AN: 152230 Hom.: 1341 Cov.: 33 AF XY: 0.126 AC XY: 9408 AN XY: 74424

Gnomad4 AFR AF: 0.0549

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0818

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.112

Alfa AF: 0.124 Hom.: 1751

Bravo AF: 0.116

Asia WGS AF: 0.224 AC: 776 AN: 3478

EpiCase AF: 0.124

EpiControl AF: 0.125

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

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	13
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.34		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3733897; hg19: chr5-134223593; COSMIC: COSV64379267; COSMIC: COSV64379267;