Variant 16-11742565-A-G 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.166T>C(p.Phe56Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,456,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

TXNDC11
NM_015914.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

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:

TXNDC11-AS1 (HGNC:56375): (TXNDC11 antisense RNA 1)

TXNDC11-AS1 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=0.043204963).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNDC11	NM_015914.7 linkuse as main transcript	c.166T>C	p.Phe56Leu	missense_variant	1/12	ENST00000283033.10	NP_056998.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNDC11	ENST00000283033.10 linkuse as main transcript	c.166T>C	p.Phe56Leu	missense_variant	1/12	2	NM_015914.7	ENSP00000283033	P2	Q6PKC3-2
TXNDC11-AS1	ENST00000572811.1 linkuse as main transcript	n.656A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000843

AC:

AN:

1304666

Hom.:

Cov.:

AF XY:

0.0000109

AC XY:

AN XY:

642720

show subpopulations

Gnomad4 AFR exome

AF:

0.000229

Gnomad4 AMR exome

AF:

0.0000830

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:

0.0000554

GnomAD4 genome

AF:

0.000118

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000174

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

Dec 14, 2022

The c.166T>C (p.F56L) alteration is located in exon 1 (coding exon 1) of the TXNDC11 gene. This alteration results from a T to C substitution at nucleotide position 166, causing the phenylalanine (F) at amino acid position 56 to be replaced by a leucine (L). 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

Pathogenic

0.60

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.55

DEOGEN2

Benign

0.013

.;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.12

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.31

N;N

REVEL

Benign

0.040

Sift

Benign

0.53

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0060

B;B

Vest4

0.067

MutPred

0.27

Gain of disorder (P = 0.0658);Gain of disorder (P = 0.0658);

MVP

0.24

MPC

0.068

ClinPred

0.042

GERP RS

3.3

Varity_R

0.16

gMVP

0.083

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