Genetic Variant NM_015914.7:c.2560G>C (chr16-11679512-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015914.7(TXNDC11):c.2560G>C(p.Ala854Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A854T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TXNDC11
NM_015914.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.927

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.081837505).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015914.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TXNDC11	NM_015914.7	MANE Select	c.2560G>C	p.Ala854Pro	missense	Exon 12 of 12	NP_056998.4
TXNDC11	NM_001303447.2		c.2641G>C	p.Ala881Pro	missense	Exon 13 of 13	NP_001290376.1	Q6PKC3-1
TXNDC11	NM_001324022.2		c.1918G>C	p.Ala640Pro	missense	Exon 11 of 11	NP_001310951.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TXNDC11	ENST00000283033.10	TSL:2 MANE Select	c.2560G>C	p.Ala854Pro	missense	Exon 12 of 12	ENSP00000283033.5	Q6PKC3-2
TXNDC11	ENST00000356957.7	TSL:1	c.2641G>C	p.Ala881Pro	missense	Exon 13 of 13	ENSP00000349439.3	Q6PKC3-1
TXNDC11	ENST00000907109.1		c.2761G>C	p.Ala921Pro	missense	Exon 14 of 14	ENSP00000577168.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1460968

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726840

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111994

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

2.4

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.016

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.80

M_CAP

Benign

0.018

MetaRNN

Benign

0.082

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.93

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.1

REVEL

Benign

0.093

Sift

Benign

0.25

Sift4G

Benign

0.15

Polyphen

0.69

Vest4

0.17

MutPred

0.17

Loss of loop (P = 0.0203)

MVP

0.38

MPC

0.20

ClinPred

0.16

GERP RS

2.6

Varity_R

0.14

gMVP

0.42

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over