NM_001098845.3:c.346A>G

Variant names:

• chr10-46383480-A-G
• rs1288547299
• NM_001098845.3:c.346A>G

Variant summary

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

The NM_001098845.3(ANXA8L1):​c.346A>G​(p.Ile116Val) 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: 𝑓 0.0 (0 hom., cov: 9)
  • Exomes 𝑓: 0.000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANXA8L1 NM_001098845.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.48
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13724458).

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.346A>G	p.Ile116Val	missense	Exon 5 of 12	NP_001092315.2	Q5VT79-1
	ANXA8L1	NM_001278924.2		c.435+788A>G		intron	N/A	NP_001265853.1	Q5VT79-2
	ANXA8L1	NM_001278923.2		c.321+788A>G		intron	N/A	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.346A>G	p.Ile116Val	missense	Exon 5 of 12	ENSP00000480221.1	Q5VT79-1
	ANXA8L1	ENST00000622769.4	TSL:1	c.435+788A>G		intron	N/A	ENSP00000483608.1	Q5VT79-2
	ANXA8L1	ENST00000584982.7	TSL:2	c.460A>G	p.Ile154Val	missense	Exon 5 of 12	ENSP00000462716.2	A0A075B752

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 69674 Hom.: 0 Cov.: 9

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000270 AC: 4 AN: 148052 AF XY: 0.0000516

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000931

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000328

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000147 AC: 12 AN: 814454 Hom.: 0 Cov.: 11 AF XY: 0.0000144 AC XY: 6 AN XY: 416036

⚠️ 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: 17832

American (AMR) AF: 0.000140 AC: 4 AN: 28636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16820

East Asian (EAS) AF: 0.0000883 AC: 3 AN: 33984

South Asian (SAS) AF: 0.00 AC: 0 AN: 61748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44680

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2686

European-Non Finnish (NFE) AF: 0.00000700 AC: 4 AN: 571608

Other (OTH) AF: 0.0000274 AC: 1 AN: 36460

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000168097), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 69674 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 33100

African (AFR) AF: 0.00 AC: 0 AN: 15106

American (AMR) AF: 0.00 AC: 0 AN: 6008

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1934

East Asian (EAS) AF: 0.00 AC: 0 AN: 2840

South Asian (SAS) AF: 0.00 AC: 0 AN: 1288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 36136

Other (OTH) AF: 0.00 AC: 0 AN: 814

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000856 AC: 1

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	0.18
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.5
Sift4G	Uncertain	0.010	D
Polyphen		0.023	B
Vest4		0.33
MutPred		0.80		Gain of MoRF binding (P = 0.0989)
MVP		0.17
ClinPred		0.16	T
GERP RS		2.1
Varity_R		0.061
gMVP		0.28
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1288547299; hg19: chr10-47754739;