chr10-46383509-G-C

Variant names:

• chr10-46383509-G-C
• NM_001098845.3:c.375G>C
• ANXA8L1 p.Lys125Asn

Variant summary

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

The NM_001098845.3(ANXA8L1):​c.375G>C​(p.Lys125Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 9)
• Consequence: ANXA8L1 NM_001098845.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05398655).

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.375G>C	p.Lys125Asn	missense	Exon 5 of 12	NP_001092315.2	Q5VT79-1
	ANXA8L1	NM_001278924.2		c.435+817G>C		intron	N/A	NP_001265853.1	Q5VT79-2
	ANXA8L1	NM_001278923.2		c.321+817G>C		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.375G>C	p.Lys125Asn	missense	Exon 5 of 12	ENSP00000480221.1	Q5VT79-1
	ANXA8L1	ENST00000622769.4	TSL:1	c.435+817G>C		intron	N/A	ENSP00000483608.1	Q5VT79-2
	ANXA8L1	ENST00000584982.7	TSL:2	c.489G>C	p.Lys163Asn	missense	Exon 5 of 12	ENSP00000462716.2	A0A075B752

Frequencies

GnomAD3 genomes Cov.: 9

GnomAD4 exome Cov.: 12

GnomAD4 genome Cov.: 9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.015	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.95	T
PhyloP100		1.0
Sift4G	Benign	1.0	T
Varity_R		0.26
gMVP		0.37
Mutation Taster		=99/1	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-47754768;