5-151108515-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001155.5(ANXA6):​c.1720G>C​(p.Val574Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

ANXA6
NM_001155.5 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.12
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3879928).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANXA6NM_001155.5 linkc.1720G>C p.Val574Leu missense_variant Exon 23 of 26 ENST00000354546.10 NP_001146.2 P08133-1A0A0S2Z2Z6
ANXA6NM_001363114.2 linkc.1702G>C p.Val568Leu missense_variant Exon 22 of 25 NP_001350043.1
ANXA6NM_001193544.2 linkc.1624G>C p.Val542Leu missense_variant Exon 22 of 25 NP_001180473.1 P08133-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANXA6ENST00000354546.10 linkc.1720G>C p.Val574Leu missense_variant Exon 23 of 26 1 NM_001155.5 ENSP00000346550.5 P08133-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.44
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
16
DANN
Benign
0.96
DEOGEN2
Benign
0.10
T;.;T;T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.70
D
LIST_S2
Uncertain
0.89
D;D;D;D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.39
T;T;T;T
MetaSVM
Benign
-0.70
T
MutationAssessor
Benign
-0.11
N;.;.;.
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.37
N;N;N;N
REVEL
Benign
0.045
Sift
Benign
0.092
T;T;T;T
Sift4G
Benign
0.54
T;T;T;T
Polyphen
0.018
B;.;.;B
Vest4
0.56
MutPred
0.68
Loss of helix (P = 0.1299);.;.;.;
MVP
0.56
MPC
0.078
ClinPred
0.48
T
GERP RS
1.8
Varity_R
0.061
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs547473117; hg19: chr5-150488076; API