10-46381163-A-G

Variant names:

• chr10-46381163-A-G
• rs1839979555
• NM_001098845.3:c.130A>G

Variant summary

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

The NM_001098845.3(ANXA8L1):​c.130A>G​(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 (★).

• Frequency:
  • Genomes: not found (cov: 5)
  • Exomes 𝑓: 0.000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANXA8L1 NM_001098845.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70

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]

ENSG00000279458 (HGNC:):

ACMG classification

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 rank	MANE	Protein	UniProt
ANXA8L1	NM_001098845.3	c.130A>G	p.Ile44Val	missense_variant	Exon 3 of 12	ENST00000619162.5	NP_001092315.2
ANXA8L1	NM_001278924.2	c.244A>G	p.Ile82Val	missense_variant	Exon 3 of 9		NP_001265853.1
ANXA8L1	NM_001278923.2	c.130A>G	p.Ile44Val	missense_variant	Exon 3 of 10		NP_001265852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA8L1	ENST00000619162.5	c.130A>G	p.Ile44Val	missense_variant	Exon 3 of 12	1	NM_001098845.3	ENSP00000480221.1

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

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

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

Submissions by phenotype

not specified Uncertain:1

Apr 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The 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
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

Other links and lift over

dbSNP: rs1839979555; hg19: chr10-47752422;