chr18-9887187-G-C

Position:

• chr18-9887187-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000357775.6(TXNDC2):​c.507G>C​(p.Glu169Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TXNDC2 ENST00000357775.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.31

Genes affected

TXNDC2 (HGNC:16470): (thioredoxin domain containing 2) Enables thioredoxin-disulfide reductase activity. Predicted to be involved in cell differentiation and cellular oxidant detoxification. Predicted to act upstream of or within cellular response to reactive oxygen species and flagellated sperm motility. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07012245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNDC2	NM_032243.6	c.507G>C	p.Glu169Asp	missense_variant	2/2	ENST00000357775.6	NP_115619.4
TXNDC2	NM_001098529.2	c.708G>C	p.Glu236Asp	missense_variant	2/2		NP_001091999.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNDC2	ENST00000357775.6	c.507G>C	p.Glu169Asp	missense_variant	2/2	1	NM_032243.6	ENSP00000350419.4
TXNDC2	ENST00000306084.6	c.708G>C	p.Glu236Asp	missense_variant	2/2	1		ENSP00000304908.6
TXNDC2	ENST00000536353.2	c.328+179G>C		intron_variant		5		ENSP00000437393.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 135

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.708G>C (p.E236D) alteration is located in exon 2 (coding exon 2) of the TXNDC2 gene. This alteration results from a G to C substitution at nucleotide position 708, causing the glutamic acid (E) at amino acid position 236 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.54
DANN	Benign	0.89
DEOGEN2	Benign	0.037	.;.;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.56	T;T;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.070	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.66	.;N;N
REVEL	Benign	0.023
Sift	Benign	0.60	.;T;T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.77	.;.;P
Vest4		0.032
MutPred		0.16		Gain of glycosylation at S237 (P = 0.0655);.;Gain of glycosylation at S237 (P = 0.0655);
MVP		0.47
MPC		0.055
ClinPred		0.25	T
GERP RS		-0.92
Varity_R		0.038
gMVP		0.019

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-9887184; COSMIC: COSV60152513; COSMIC: COSV60152513;