rs767215473

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001155.5(ANXA6):​c.1593A>T​(p.Glu531Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,886 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. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ANXA6
NM_001155.5 missense, splice_region

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.802
Variant links:
Genes affected
ANXA6 (HGNC:544): (annexin A6) Annexin VI belongs to a family of calcium-dependent membrane and phospholipid binding proteins. Several members of the annexin family have been implicated in membrane-related events along exocytotic and endocytotic pathways. The annexin VI gene is approximately 60 kbp long and contains 26 exons. It encodes a protein of about 68 kDa that consists of eight 68-amino acid repeats separated by linking sequences of variable lengths. It is highly similar to human annexins I and II sequences, each of which contain four such repeats. Annexin VI has been implicated in mediating the endosome aggregation and vesicle fusion in secreting epithelia during exocytosis. Alternatively spliced transcript variants have been described. [provided by RefSeq, Aug 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16496935).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANXA6NM_001155.5 linkc.1593A>T p.Glu531Asp missense_variant, splice_region_variant Exon 22 of 26 ENST00000354546.10 NP_001146.2 P08133-1A0A0S2Z2Z6
ANXA6NM_001363114.2 linkc.1575A>T p.Glu525Asp missense_variant, splice_region_variant Exon 21 of 25 NP_001350043.1
ANXA6NM_001193544.2 linkc.1497A>T p.Glu499Asp missense_variant, splice_region_variant Exon 21 of 25 NP_001180473.1 P08133-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANXA6ENST00000354546.10 linkc.1593A>T p.Glu531Asp missense_variant, splice_region_variant Exon 22 of 26 1 NM_001155.5 ENSP00000346550.5 P08133-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000872
AC:
2
AN:
229250
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
124020
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000615
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:
0.00000138
AC:
2
AN:
1446886
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
718886
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000463
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.:
32
Bravo
AF:
0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
T;.;T;T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.53
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Benign
0.76
T;T;T;T
M_CAP
Benign
0.0070
T
MetaRNN
Benign
0.16
T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.1
L;.;.;.
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.88
N;N;N;N
REVEL
Benign
0.18
Sift
Uncertain
0.027
D;D;D;T
Sift4G
Benign
0.21
T;T;T;T
Polyphen
0.038
B;.;.;P
Vest4
0.25
MutPred
0.39
Gain of helix (P = 0.132);.;.;.;
MVP
0.44
MPC
0.079
ClinPred
0.45
T
GERP RS
-1.5
Varity_R
0.24
gMVP
0.28

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.

Other links and lift over

dbSNP: rs767215473; hg19: chr5-150489405; API