16-11679437-C-T

Position:

• chr16-11679437-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015914.7(TXNDC11):​c.2635G>A​(p.Glu879Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TXNDC11 NM_015914.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.39

Genes affected

TXNDC11 (HGNC:28030): (thioredoxin domain containing 11) Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TXNDC11 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3357654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNDC11	NM_015914.7	c.2635G>A	p.Glu879Lys	missense_variant	12/12	ENST00000283033.10	NP_056998.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNDC11	ENST00000283033.10	c.2635G>A	p.Glu879Lys	missense_variant	12/12	2	NM_015914.7	ENSP00000283033.5
TXNDC11	ENST00000356957.7	c.2716G>A	p.Glu906Lys	missense_variant	13/13	1		ENSP00000349439.3
TXNDC11	ENST00000570917.5	n.845G>A		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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 17, 2021

The c.2635G>A (p.E879K) alteration is located in exon 12 (coding exon 12) of the TXNDC11 gene. This alteration results from a G to A substitution at nucleotide position 2635, causing the glutamic acid (E) at amino acid position 879 to be replaced by a lysine (K). 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	0.29
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.029	.;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.88	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.011	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.35
MutPred		0.34		.;Gain of MoRF binding (P = 0.0065);
MVP		0.59
MPC		0.14
ClinPred		0.87	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.37
gMVP		0.35

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: rs1278059856; hg19: chr16-11773293;