chr16-11679427-T-C

Position:

• chr16-11679427-T-C

Variant summary

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

The NM_015914.7(TXNDC11):​c.2645A>G​(p.Asp882Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TXNDC11 NM_015914.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20742166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNDC11	NM_015914.7	c.2645A>G	p.Asp882Gly	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.2645A>G	p.Asp882Gly	missense_variant	12/12	2	NM_015914.7	ENSP00000283033.5
TXNDC11	ENST00000356957.7	c.2726A>G	p.Asp909Gly	missense_variant	13/13	1		ENSP00000349439.3
TXNDC11	ENST00000570917.5	n.855A>G		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

Nov 30, 2022

The c.2645A>G (p.D882G) alteration is located in exon 12 (coding exon 12) of the TXNDC11 gene. This alteration results from a A to G substitution at nucleotide position 2645, causing the aspartic acid (D) at amino acid position 882 to be replaced by a glycine (G). 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	0.23
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.047	.;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.065
Sift	Benign	0.054	T;D
Sift4G	Uncertain	0.053	T;T
Polyphen		0.86	P;P
Vest4		0.30
MutPred		0.29		.;Loss of loop (P = 0.0112);
MVP		0.54
MPC		0.091
ClinPred		0.53	D
GERP RS		2.0
Varity_R		0.088
gMVP		0.32

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: chr16-11773283;