14-52431358-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020784.3(TXNDC16):c.*946T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0955 in 152,260 control chromosomes in the GnomAD database, including 813 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 0.096 (813 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: TXNDC16 NM_020784.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342

Genes affected

TXNDC16 (HGNC:19965): (thioredoxin domain containing 16) Located in endoplasmic reticulum lumen. [provided by Alliance of Genome Resources, Apr 2022]

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 (EAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNDC16	NM_020784.3	c.*946T>C		3_prime_UTR_variant	21/21	ENST00000281741.9
TXNDC16	NM_001160047.2	c.*946T>C		3_prime_UTR_variant	21/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNDC16	ENST00000281741.9	c.*946T>C		3_prime_UTR_variant	21/21	1	NM_020784.3	P1

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14546 AN: 152142 Hom.: 813 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.0566

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0708

Gnomad OTH AF: 0.100

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0955 AC: 14543 AN: 152260 Hom.: 813 Cov.: 33 AF XY: 0.0946 AC XY: 7040 AN XY: 74452

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.0660

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.0344

Gnomad4 FIN AF: 0.0566

Gnomad4 NFE AF: 0.0709

Gnomad4 OTH AF: 0.0989

Alfa AF: 0.0755 Hom.: 479

Bravo AF: 0.107

Asia WGS AF: 0.102 AC: 353 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	1.2
Dann	Benign	0.64

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: rs1565970; hg19: chr14-52898076;