rs745379492

Variant summary

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

The NM_001155.5(ANXA6):​c.1819A>G​(p.Lys607Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,656 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: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

ANXA6
NM_001155.5 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.67
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.1819A>G p.Lys607Glu missense_variant Exon 24 of 26 ENST00000354546.10 NP_001146.2 P08133-1A0A0S2Z2Z6
ANXA6NM_001363114.2 linkc.1801A>G p.Lys601Glu missense_variant Exon 23 of 25 NP_001350043.1
ANXA6NM_001193544.2 linkc.1723A>G p.Lys575Glu missense_variant Exon 23 of 25 NP_001180473.1 P08133-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANXA6ENST00000354546.10 linkc.1819A>G p.Lys607Glu missense_variant Exon 24 of 26 1 NM_001155.5 ENSP00000346550.5 P08133-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461656
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727114
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T;.;T;T
Eigen
Benign
0.055
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.83
T;T;T;T
M_CAP
Benign
0.0086
T
MetaRNN
Uncertain
0.46
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.40
N;.;.;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-0.55
N;N;N;N
REVEL
Benign
0.16
Sift
Benign
0.069
T;T;D;D
Sift4G
Uncertain
0.0090
D;D;D;D
Polyphen
0.14
B;.;.;P
Vest4
0.55
MutPred
0.61
Gain of ubiquitination at K610 (P = 0.0303);.;.;.;
MVP
0.48
MPC
0.20
ClinPred
0.66
D
GERP RS
5.1
Varity_R
0.38
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-150484826; API