14-52457135-C-A

Variant names:

• chr14-52457135-C-A
• rs754734150
• NM_020784.3:c.1658G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020784.3(TXNDC16):​c.1658G>T​(p.Gly553Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,440,498 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G553E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TXNDC16 NM_020784.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.83
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020784.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC16	NM_020784.3	MANE Select	c.1658G>T	p.Gly553Val	missense	Exon 17 of 21	NP_065835.2	Q9P2K2
	TXNDC16	NM_001160047.2		c.1643G>T	p.Gly548Val	missense	Exon 17 of 21	NP_001153519.1	B7ZME4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC16	ENST00000281741.9	TSL:1 MANE Select	c.1658G>T	p.Gly553Val	missense	Exon 17 of 21	ENSP00000281741.4	Q9P2K2
	TXNDC16	ENST00000936707.1		c.1658G>T	p.Gly553Val	missense	Exon 17 of 21	ENSP00000606766.1
	TXNDC16	ENST00000956219.1		c.1658G>T	p.Gly553Val	missense	Exon 18 of 22	ENSP00000626278.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000433 AC: 1 AN: 230770 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1440498 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 716332

African (AFR) AF: 0.0000312 AC: 1 AN: 32038

American (AMR) AF: 0.00 AC: 0 AN: 39810

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25670

East Asian (EAS) AF: 0.00 AC: 0 AN: 38406

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81470

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104614

Other (OTH) AF: 0.00 AC: 0 AN: 59530

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.8
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.54		Gain of methylation at K552 (P = 0.0415)
MVP		0.72
MPC		0.18
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.72
gMVP		0.78
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs754734150; hg19: chr14-52923853;