10-80169007-C-T

Variant names:

Variant summary

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

The NM_145868.2(ANXA11):c.523G>A(p.Gly175Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,394,658 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ANXA11
NM_145868.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 1.69

Publications

3 publications found

Variant links:

Genes affected

ANXA11 (HGNC:535): (annexin A11) This gene encodes a member of the annexin family, a group of calcium-dependent phospholipid-binding proteins. Annexins have unique N-terminal domains and conserved C-terminal domains, which contain calcium-dependent phospholipid-binding sites. The encoded protein is a 56-kD antigen recognized by sera from patients with various autoimmune diseases. Several transcript variants encoding two different isoforms have been identified. [provided by RefSeq, Dec 2015]

ANXA11 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis type 23
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
inclusion body myopathy and brain white matter abnormalities
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ANXA11 links:

Genome browser will be placed here

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=0.1568383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA11	NM_145868.2 link	c.523G>A	p.Gly175Arg	missense_variant	Exon 5 of 16	ENST00000422982.8	NP_665875.1	P50995-1Q5T0G8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA11	ENST00000422982.8 link	c.523G>A	p.Gly175Arg	missense_variant	Exon 5 of 16	1	NM_145868.2	ENSP00000404412.2		P50995-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

180244

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000143

AC:

AN:

1394658

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

688738

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30980

American (AMR)

AF:

0.00

AC:

AN:

31640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21248

East Asian (EAS)

AF:

0.00

AC:

AN:

39004

South Asian (SAS)

AF:

0.00

AC:

AN:

73796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5300

European-Non Finnish (NFE)

AF:

0.00000184

AC:

AN:

1084338

Other (OTH)

AF:

0.00

AC:

AN:

57382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Amyotrophic lateral sclerosis type 23

Pathogenic:1

Jan 29, 2018

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Uncertain:1

Mar 14, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 175 of the ANXA11 protein (p.Gly175Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with amyotrophic lateral sclerosis (PMID: 28469040). ClinVar contains an entry for this variant (Variation ID: 488355). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;.;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.79

.;.;T;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.4

M;M;.;M

PhyloP100

1.7

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Benign

0.036

Sift

Benign

0.10

T;T;T;T

Sift4G

Benign

0.11

T;T;D;T

Polyphen

0.0

B;B;.;B

Vest4

0.35

MutPred

0.28

Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);.;Loss of sheet (P = 0.0228);

MVP

0.13

MPC

0.38

ClinPred

0.28

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.062

gMVP

0.58

Mutation Taster

=2/98

disease causing (ClinVar)

(source)

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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10-80169007-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over