rs28759013

Positions:

• chr14-52519279-C-T

Variant summary

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

The NM_020784.3(TXNDC16):​c.407G>A​(p.Ser136Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00638 in 1,595,622 control chromosomes in the GnomAD database, including 529 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.035 (269 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (260 hom.)
• Consequence: TXNDC16 NM_020784.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.86

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 (MetaRNN=0.0014813244).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNDC16	NM_020784.3	c.407G>A	p.Ser136Asn	missense_variant	7/21	ENST00000281741.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNDC16	ENST00000281741.9	c.407G>A	p.Ser136Asn	missense_variant	7/21	1	NM_020784.3	P1
TXNDC16	ENST00000557374.1	c.-294-28274G>A		intron_variant		4
TXNDC16	ENST00000554399.1	n.207+33037G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5242 AN: 151972 Hom.: 268 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.0282

GnomAD3 exomes AF: 0.00877 AC: 2165 AN: 247004 Hom.: 105 AF XY: 0.00626 AC XY: 837 AN XY: 133648

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.00602

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000271

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000356

Gnomad OTH exome AF: 0.00551

GnomAD4 exome AF: 0.00341 AC: 4920 AN: 1443532 Hom.: 260 Cov.: 28 AF XY: 0.00294 AC XY: 2111 AN XY: 718986

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.00731

Gnomad4 ASJ exome AF: 0.0000773

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000319

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000195

Gnomad4 OTH exome AF: 0.00727

GnomAD4 genome AF: 0.0346 AC: 5261 AN: 152090 Hom.: 269 Cov.: 32 AF XY: 0.0331 AC XY: 2460 AN XY: 74342

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.00589 Hom.: 61

Bravo AF: 0.0394

ESP6500AA AF: 0.117 AC: 514

ESP6500EA AF: 0.000816 AC: 7

ExAC AF: 0.0112 AC: 1363

Asia WGS AF: 0.00868 AC: 31 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	17
DANN	Benign	0.40
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.5	N
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.21
MPC		0.019
ClinPred		0.0060	T
GERP RS		5.6
Varity_R		0.053
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs28759013; hg19: chr14-52985997;