10-46379957-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001098845.3(ANXA8L1):​c.94A>C​(p.Lys32Gln) variant causes a missense change. In-silico tool predicts 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: 0)

Consequence

ANXA8L1
NM_001098845.3 missense

Scores

3
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.75
Variant links:
Genes affected
ANXA8L1 (HGNC:23334): (annexin A8 like 1) This gene encodes a member of the annexin family of evolutionarily conserved Ca2+ and phospholipid binding proteins. The encoded protein may function as an an anticoagulant that indirectly inhibits the thromboplastin-specific complex. Overexpression of this gene has been associated with acute myelocytic leukemia. A highly similar duplicated copy of this gene is found in close proximity on the long arm of chromosome 10. [provided by RefSeq, Apr 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.01755476).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANXA8L1NM_001098845.3 linkc.94A>C p.Lys32Gln missense_variant Exon 2 of 12 ENST00000619162.5 NP_001092315.2 P13928Q5VT79-1
ANXA8L1NM_001278924.2 linkc.94A>C p.Lys32Gln missense_variant Exon 2 of 9 NP_001265853.1 Q5VT79-2
ANXA8L1NM_001278923.2 linkc.94A>C p.Lys32Gln missense_variant Exon 2 of 10 NP_001265852.1 B4DTF2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANXA8L1ENST00000619162.5 linkc.94A>C p.Lys32Gln missense_variant Exon 2 of 12 1 NM_001098845.3 ENSP00000480221.1 Q5VT79-1

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD3 exomes
AF:
0.000111
AC:
9
AN:
80884
Hom.:
0
AF XY:
0.0000741
AC XY:
3
AN XY:
40468
show subpopulations
Gnomad AFR exome
AF:
0.00130
Gnomad AMR exome
AF:
0.00
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
Cov.:
0
GnomAD4 genome
Cov.:
0
ExAC
AF:
0.000135
AC:
11

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.94A>C (p.K32Q) alteration is located in exon 2 (coding exon 2) of the ANXA8L2 gene. This alteration results from a A to C substitution at nucleotide position 94, causing the lysine (K) at amino acid position 32 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.10
T;.;T;.
Eigen
Benign
-0.029
Eigen_PC
Benign
-0.034
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.61
T;T;T;T
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.018
T;T;T;T
MetaSVM
Benign
-0.76
T
Sift4G
Uncertain
0.023
D;D;D;D
Polyphen
0.016, 0.0080, 0.0010
.;B;B;B
Vest4
0.22
MutPred
0.63
Loss of ubiquitination at K32 (P = 0.027);Loss of ubiquitination at K32 (P = 0.027);Loss of ubiquitination at K32 (P = 0.027);Loss of ubiquitination at K32 (P = 0.027);
MVP
0.19
ClinPred
0.085
T
GERP RS
2.6
Varity_R
0.093
gMVP
0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2670516; hg19: chr10-47751217; API