rs61740050

Variant names:

• chr14-52439324-C-A
• rs61740050
• NM_020784.3:c.2074G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-52439324-C-A
• chr14-52439324-C-G
• chr14-52439324-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020784.3(TXNDC16):​c.2074G>T​(p.Val692Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. V692I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TXNDC16 NM_020784.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534
• Publications: 1 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.747

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.2074G>T	p.Val692Phe	missense	Exon 20 of 21	NP_065835.2	Q9P2K2
	TXNDC16	NM_001160047.2		c.2059G>T	p.Val687Phe	missense	Exon 20 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.2074G>T	p.Val692Phe	missense	Exon 20 of 21	ENSP00000281741.4	Q9P2K2
	TXNDC16	ENST00000936707.1		c.2074G>T	p.Val692Phe	missense	Exon 20 of 21	ENSP00000606766.1
	TXNDC16	ENST00000956219.1		c.2074G>T	p.Val692Phe	missense	Exon 21 of 22	ENSP00000626278.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 250974 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

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: 6.84e-7 AC: 1 AN: 1461722 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727148

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60380

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.53
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.22
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.018	D
Polyphen		0.99	D
Vest4		0.66
MutPred		0.50		Gain of sheet (P = 0.0344)
MVP		0.69
MPC		0.15
ClinPred		0.95	D
GERP RS		2.4
Varity_R		0.35
gMVP		0.80
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: -22

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

Other links and lift over

dbSNP: rs61740050; hg19: chr14-52906042;