10-46381163-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 11/17 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098845.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA8L1	NM_001098845.3	MANE Select	c.130A>G	p.Ile44Val	missense	Exon 3 of 12	NP_001092315.2	Q5VT79-1
	ANXA8L1	NM_001278924.2		c.244A>G	p.Ile82Val	missense	Exon 3 of 9	NP_001265853.1	Q5VT79-2
	ANXA8L1	NM_001278923.2		c.130A>G	p.Ile44Val	missense	Exon 3 of 10	NP_001265852.1	B4DTF2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA8L1	ENST00000619162.5	TSL:1 MANE Select	c.130A>G	p.Ile44Val	missense	Exon 3 of 12	ENSP00000480221.1	Q5VT79-1
	ANXA8L1	ENST00000622769.4	TSL:1	c.244A>G	p.Ile82Val	missense	Exon 3 of 9	ENSP00000483608.1	Q5VT79-2
	ANXA8L1	ENST00000584982.7	TSL:2	c.244A>G	p.Ile82Val	missense	Exon 3 of 12	ENSP00000462716.2	A0A075B752

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD2 exomes AF: 0.000336 AC: 25 AN: 74490 AF XY: 0.000589

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 7436

American (AMR) AF: 0.00 AC: 0 AN: 19646

Ashkenazi Jewish (ASJ) AF: 0.000283 AC: 4 AN: 14114

East Asian (EAS) AF: 0.0000600 AC: 2 AN: 33328

South Asian (SAS) AF: 0.00 AC: 0 AN: 55836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2012

European-Non Finnish (NFE) AF: 0.00000521 AC: 2 AN: 383660

Other (OTH) AF: 0.00 AC: 0 AN: 27080

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 5

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000854 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.7
Sift4G	Benign	0.063	T
Polyphen		0.011	B
Vest4		0.34
MutPred		0.69		Gain of loop (P = 0.1069)
MVP		0.061
ClinPred		0.049	T
GERP RS		1.1
Varity_R		0.027
gMVP		0.32
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1839979555; hg19: chr10-47752422;