chr10-46381163-A-G

Variant summary

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

The ENST00000619162.5(ANXA8L1):ā€‹c.130A>Gā€‹(p.Ile44Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 5)
Exomes š‘“: 0.000014 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ANXA8L1
ENST00000619162.5 missense

Scores

2
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.014364302).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ANXA8L1NM_001098845.3 linkuse as main transcriptc.130A>G p.Ile44Val missense_variant 3/12 ENST00000619162.5 NP_001092315.2
ANXA8L1NM_001278924.2 linkuse as main transcriptc.244A>G p.Ile82Val missense_variant 3/9 NP_001265853.1
ANXA8L1NM_001278923.2 linkuse as main transcriptc.130A>G p.Ile44Val missense_variant 3/10 NP_001265852.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ANXA8L1ENST00000619162.5 linkuse as main transcriptc.130A>G p.Ile44Val missense_variant 3/121 NM_001098845.3 ENSP00000480221 P1Q5VT79-1

Frequencies

GnomAD3 genomes
Cov.:
5
GnomAD3 exomes
AF:
0.000336
AC:
25
AN:
74490
Hom.:
3
AF XY:
0.000589
AC XY:
22
AN XY:
37342
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00762
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000750
Gnomad OTH exome
AF:
0.000868
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000139
AC:
8
AN:
573570
Hom.:
0
Cov.:
8
AF XY:
0.0000134
AC XY:
4
AN XY:
299450
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000283
Gnomad4 EAS exome
AF:
0.0000600
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000521
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
5
ExAC
AF:
0.0000854
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 05, 2023The c.130A>G (p.I44V) alteration is located in exon 3 (coding exon 3) of the ANXA8L2 gene. This alteration results from a A to G substitution at nucleotide position 130, causing the isoleucine (I) at amino acid position 44 to be replaced by a valine (V). 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
0.11
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.027
T;.;T;.
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.63
D
LIST_S2
Uncertain
0.86
D;D;D;D
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.014
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
D;N;N;N
Sift4G
Benign
0.063
T;T;T;T
Polyphen
0.011, 0.0, 0.0010
.;B;B;B
Vest4
0.34
MutPred
0.69
.;.;Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MVP
0.061
ClinPred
0.049
T
GERP RS
1.1
Varity_R
0.027
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1839979555; hg19: chr10-47752422; API