rs2670516

Variant names:

• chr10-46379957-A-C
• rs2670516
• NM_001098845.3:c.94A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001098845.3(ANXA8L1):​c.94A>C​(p.Lys32Gln) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: ANXA8L1 NM_001098845.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.75
• 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=0.01755476).

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.94A>C	p.Lys32Gln	missense	Exon 2 of 12	NP_001092315.2	Q5VT79-1
	ANXA8L1	NM_001278924.2		c.94A>C	p.Lys32Gln	missense	Exon 2 of 9	NP_001265853.1	Q5VT79-2
	ANXA8L1	NM_001278923.2		c.94A>C	p.Lys32Gln	missense	Exon 2 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.94A>C	p.Lys32Gln	missense	Exon 2 of 12	ENSP00000480221.1	Q5VT79-1
	ANXA8L1	ENST00000622769.4	TSL:1	c.94A>C	p.Lys32Gln	missense	Exon 2 of 9	ENSP00000483608.1	Q5VT79-2
	ANXA8L1	ENST00000584982.7	TSL:2	c.94A>C	p.Lys32Gln	missense	Exon 2 of 12	ENSP00000462716.2	A0A075B752

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.000111 AC: 9 AN: 80884 AF XY: 0.0000741

Gnomad AFR exome AF: 0.00130

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000135 AC: 11

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	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.029
Eigen_PC	Benign	-0.034
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.76	T
PhyloP100		3.8
Sift4G	Uncertain	0.023	D
Polyphen		0.016	B
Vest4		0.22
MutPred		0.63		Loss of ubiquitination at K32 (P = 0.027)
MVP		0.19
ClinPred		0.085	T
GERP RS		2.6
Varity_R		0.093
gMVP		0.48

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: rs2670516; hg19: chr10-47751217;