Variant 16-11679218-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015914.7(TXNDC11):c.2854A>G(p.Asn952Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,592 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

TXNDC11
NM_015914.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.97

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051089406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNDC11	NM_015914.7 linkuse as main transcript	c.2854A>G	p.Asn952Asp	missense_variant	12/12	ENST00000283033.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNDC11	ENST00000283033.10 linkuse as main transcript	c.2854A>G	p.Asn952Asp	missense_variant	12/12	2	NM_015914.7	P2	Q6PKC3-2
TXNDC11	ENST00000356957.7 linkuse as main transcript	c.2935A>G	p.Asn979Asp	missense_variant	13/13	1		A2	Q6PKC3-1
TXNDC11	ENST00000570917.5 linkuse as main transcript	n.1064A>G		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000518

AC:

AN:

250856

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000821

AC:

AN:

1461592

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.2854A>G (p.N952D) 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 2854, causing the asparagine (N) at amino acid position 952 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

0.10

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.012

.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.051

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.48

N;N

REVEL

Benign

0.085

Sift

Benign

0.38

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.095

B;B

Vest4

0.080

MutPred

0.096

.;Loss of MoRF binding (P = 0.0386);

MVP

0.42

MPC

0.089

ClinPred

0.063

GERP RS

5.6

Varity_R

0.10

gMVP

0.054

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over