chr10-80155890-C-A

Variant names:

• chr10-80155890-C-A
• rs1318489141
• NM_145868.2:c.1481G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145868.2(ANXA11):​c.1481G>T​(p.Arg494Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R494Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANXA11 NM_145868.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 3 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA11	NM_145868.2	c.1481G>T	p.Arg494Leu	missense_variant	Exon 16 of 16	ENST00000422982.8	NP_665875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA11	ENST00000422982.8	c.1481G>T	p.Arg494Leu	missense_variant	Exon 16 of 16	1	NM_145868.2	ENSP00000404412.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.065	T;T;.;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.58	.;.;T;T
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.3	M;M;.;M
PhyloP100		1.7
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-4.5	D;D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.98	D;D;.;D
Vest4		0.43
MutPred		0.63		Loss of disorder (P = 0.0781);Loss of disorder (P = 0.0781);.;Loss of disorder (P = 0.0781);
MVP		0.26
MPC		0.31
ClinPred		1.0	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.58
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1318489141; hg19: chr10-81915646;