10-46381211-G-A

Variant names:

• chr10-46381211-G-A
• rs1839980223
• NM_001098845.3:c.178G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001098845.3(ANXA8L1):​c.178G>A​(p.Ala60Thr) 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: 0.000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANXA8L1 NM_001098845.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.03
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13279685).

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.178G>A	p.Ala60Thr	missense	Exon 3 of 12	NP_001092315.2	Q5VT79-1
	ANXA8L1	NM_001278924.2		c.292G>A	p.Ala98Thr	missense	Exon 3 of 9	NP_001265853.1	Q5VT79-2
	ANXA8L1	NM_001278923.2		c.178G>A	p.Ala60Thr	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.178G>A	p.Ala60Thr	missense	Exon 3 of 12	ENSP00000480221.1	Q5VT79-1
	ANXA8L1	ENST00000622769.4	TSL:1	c.292G>A	p.Ala98Thr	missense	Exon 3 of 9	ENSP00000483608.1	Q5VT79-2
	ANXA8L1	ENST00000584982.7	TSL:2	c.292G>A	p.Ala98Thr	missense	Exon 3 of 12	ENSP00000462716.2	A0A075B752

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD2 exomes AF: 0.000310 AC: 20 AN: 64498 AF XY: 0.000311

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000960

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000887

Gnomad OTH exome AF: 0.000948

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000106 AC: 7 AN: 660290 Hom.: 0 Cov.: 9 AF XY: 0.0000175 AC XY: 6 AN XY: 342268

⚠️ 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: 7868

American (AMR) AF: 0.00 AC: 0 AN: 18644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14900

East Asian (EAS) AF: 0.00 AC: 0 AN: 34456

South Asian (SAS) AF: 0.0000166 AC: 1 AN: 60130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2168

European-Non Finnish (NFE) AF: 0.0000130 AC: 6 AN: 459964

Other (OTH) AF: 0.00 AC: 0 AN: 30248

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000226914), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 5

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000641 AC: 2

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	0.14
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.029
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.0
Sift4G	Benign	0.43	T
Polyphen		1.0	D
Vest4		0.44
MutPred		0.28		Gain of phosphorylation at A60 (P = 0.0618)
MVP		0.092
ClinPred		0.14	T
GERP RS		2.3
Varity_R		0.027
gMVP		0.22
Mutation Taster		=100/0	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: rs1839980223; hg19: chr10-47752470;