NM_001155.5:c.1639T>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001155.5(ANXA6):​c.1639T>A​(p.Phe547Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,611,544 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ANXA6
NM_001155.5 missense

Scores

4
8
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.39
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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
ANXA6NM_001155.5 linkc.1639T>A p.Phe547Ile missense_variant Exon 22 of 26 ENST00000354546.10 NP_001146.2 P08133-1A0A0S2Z2Z6
ANXA6NM_001363114.2 linkc.1621T>A p.Phe541Ile missense_variant Exon 21 of 25 NP_001350043.1
ANXA6NM_001193544.2 linkc.1543T>A p.Phe515Ile missense_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.1639T>A p.Phe547Ile missense_variant Exon 22 of 26 1 NM_001155.5 ENSP00000346550.5 P08133-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152140
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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
GnomAD3 exomes
AF:
0.0000571
AC:
14
AN:
245018
Hom.:
0
AF XY:
0.0000677
AC XY:
9
AN XY:
132902
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000381
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:
0.000167
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1459404
Hom.:
0
Cov.:
30
AF XY:
0.0000152
AC XY:
11
AN XY:
725774
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000337
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:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152140
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
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
Bravo
AF:
0.0000189
ExAC
AF:
0.0000414
AC:
5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.72
BayesDel_addAF
Benign
-0.066
T
BayesDel_noAF
Uncertain
-0.020
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.22
T;.;T;T
Eigen
Pathogenic
0.69
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.95
D;D;D;D
M_CAP
Benign
0.024
T
MetaRNN
Uncertain
0.73
D;D;D;D
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.7
M;.;.;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-2.1
N;N;D;D
REVEL
Benign
0.28
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D
Polyphen
1.0
D;.;.;D
Vest4
0.78
MutPred
0.67
Gain of MoRF binding (P = 0.1342);.;.;.;
MVP
0.69
MPC
0.49
ClinPred
0.46
T
GERP RS
4.5
Varity_R
0.71
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs757739987; hg19: chr5-150489359; API