dbSNP rs1839979555: ANXA8L1:p.Ile44Leu (chr10-46381163-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001098845.3(ANXA8L1):c.130A>C(p.Ile44Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I44V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000049 ( 0 hom., cov: 5)

Exomes 𝑓: 0.000012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANXA8L1
NM_001098845.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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]

ANXA8L1 links:

ENSG00000279458 (HGNC:):

ENSG00000279458 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15743494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA8L1	NM_001098845.3 link	c.130A>C	p.Ile44Leu	missense_variant	Exon 3 of 12	ENST00000619162.5	NP_001092315.2	P13928Q5VT79-1
ANXA8L1	NM_001278924.2 link	c.244A>C	p.Ile82Leu	missense_variant	Exon 3 of 9		NP_001265853.1	Q5VT79-2
ANXA8L1	NM_001278923.2 link	c.130A>C	p.Ile44Leu	missense_variant	Exon 3 of 10		NP_001265852.1	B4DTF2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA8L1	ENST00000619162.5 link	c.130A>C	p.Ile44Leu	missense_variant	Exon 3 of 12	1	NM_001098845.3	ENSP00000480221.1		Q5VT79-1

Frequencies

GnomAD3 genomes

AF:

0.0000494

AC:

AN:

40462

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000324

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000429

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000122

AC:

AN:

573568

Hom.:

Cov.:

AF XY:

0.00000668

AC XY:

AN XY:

299448

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:

0.0000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000494

AC:

AN:

40462

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

19100

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000324

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000429

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.034

T;.;T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.0085

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-1.0

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.44, 0.0030, 0.066

.;B;B;B

Vest4

0.47

MutPred

0.61

.;.;Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);

MVP

0.055

ClinPred

0.34

GERP RS

1.1

Varity_R

0.066

gMVP

0.53

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over