10-46390898-G-A

Variant names:

• chr10-46390898-G-A
• rs1554975591
• NM_001098845.3:c.952G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001098845.3(ANXA8L1):​c.952G>A​(p.Ala318Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 16)
  • Exomes 𝑓: 0.0000016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANXA8L1 NM_001098845.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.27
• 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]

ENSG00000285402 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.952G>A	p.Ala318Thr	missense	Exon 12 of 12	NP_001092315.2	Q5VT79-1
	ANXA8L1	NM_001278924.2		c.799G>A	p.Ala267Thr	missense	Exon 9 of 9	NP_001265853.1	Q5VT79-2
	ANXA8L1	NM_001278923.2		c.781G>A	p.Ala261Thr	missense	Exon 10 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.952G>A	p.Ala318Thr	missense	Exon 12 of 12	ENSP00000480221.1	Q5VT79-1
	ANXA8L1	ENST00000622769.4	TSL:1	c.799G>A	p.Ala267Thr	missense	Exon 9 of 9	ENSP00000483608.1	Q5VT79-2
	ANXA8L1	ENST00000584982.7	TSL:2	c.1066G>A	p.Ala356Thr	missense	Exon 12 of 12	ENSP00000462716.2	A0A075B752

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD2 exomes AF: 0.00000455 AC: 1 AN: 219918 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000108

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000156 AC: 2 AN: 1281804 Hom.: 0 Cov.: 30 AF XY: 0.00000157 AC XY: 1 AN XY: 635954

African (AFR) AF: 0.00 AC: 0 AN: 31218

American (AMR) AF: 0.00 AC: 0 AN: 40246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21668

East Asian (EAS) AF: 0.00 AC: 0 AN: 39284

South Asian (SAS) AF: 0.00 AC: 0 AN: 78186

European-Finnish (FIN) AF: 0.0000232 AC: 1 AN: 43080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3622

European-Non Finnish (NFE) AF: 0.00000103 AC: 1 AN: 971920

Other (OTH) AF: 0.00 AC: 0 AN: 52580

GnomAD4 genome Cov.: 16

Alfa AF: 0.00 Hom.: 0

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	0.21
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.080
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0090	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.3
Sift4G	Benign	0.091	T
Polyphen		1.0	D
Vest4		0.56
MutPred		0.48		Gain of disorder (P = 0.0518)
MVP		0.21
ClinPred		0.93	D
GERP RS		1.9
Varity_R		0.044
gMVP		0.25

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

Other links and lift over

dbSNP: rs1554975591; hg19: chr10-47762155; COSMIC: COSV63225737;