rs199792826

Variant names:

• chr14-52432506-C-G
• rs199792826
• NM_020784.3:c.2276G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-52432506-C-G
• chr14-52432506-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020784.3(TXNDC16):​c.2276G>C​(p.Arg759Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R759H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TXNDC16 NM_020784.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049200118).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNDC16	NM_020784.3	c.2276G>C	p.Arg759Pro	missense_variant	Exon 21 of 21	ENST00000281741.9	NP_065835.2
TXNDC16	NM_001160047.2	c.2261G>C	p.Arg754Pro	missense_variant	Exon 21 of 21		NP_001153519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNDC16	ENST00000281741.9	c.2276G>C	p.Arg759Pro	missense_variant	Exon 21 of 21	1	NM_020784.3	ENSP00000281741.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251168 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135764

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461672 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727134

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.9
DANN	Benign	0.63
DEOGEN2	Benign	0.00061	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.71	N
REVEL	Benign	0.013
Sift	Benign	0.28	T
Sift4G	Benign	0.24	T
Polyphen		0.016	B
Vest4		0.039
MutPred		0.45		Loss of MoRF binding (P = 9e-04);
MVP		0.15
MPC		0.022
ClinPred		0.030	T
GERP RS		-0.20
Varity_R		0.096
gMVP		0.29

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: rs199792826; hg19: chr14-52899224;