10-46385447-C-A

Variant names:

• chr10-46385447-C-A
• rs1331876224
• NM_001098845.3:c.620C>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.620C>A​(p.Thr207Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T207M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 14)
  • Exomes 𝑓: 0.0000028 (1 hom.)
• Consequence: ANXA8L1 NM_001098845.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248
• 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=0.1623714).

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.620C>A	p.Thr207Lys	missense	Exon 8 of 12	NP_001092315.2	Q5VT79-1
	ANXA8L1	NM_001278924.2		c.563C>A	p.Thr188Lys	missense	Exon 6 of 9	NP_001265853.1	Q5VT79-2
	ANXA8L1	NM_001278923.2		c.449C>A	p.Thr150Lys	missense	Exon 6 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.620C>A	p.Thr207Lys	missense	Exon 8 of 12	ENSP00000480221.1	Q5VT79-1
	ANXA8L1	ENST00000622769.4	TSL:1	c.563C>A	p.Thr188Lys	missense	Exon 6 of 9	ENSP00000483608.1	Q5VT79-2
	ANXA8L1	ENST00000584982.7	TSL:2	c.734C>A	p.Thr245Lys	missense	Exon 8 of 12	ENSP00000462716.2	A0A075B752

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD4 exome AF: 0.00000282 AC: 3 AN: 1064054 Hom.: 1 Cov.: 20 AF XY: 0.00000373 AC XY: 2 AN XY: 536370

⚠️ 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: 20922

American (AMR) AF: 0.00 AC: 0 AN: 34734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21018

East Asian (EAS) AF: 0.00 AC: 0 AN: 39364

South Asian (SAS) AF: 0.0000274 AC: 2 AN: 72986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3294

European-Non Finnish (NFE) AF: 0.00000127 AC: 1 AN: 784724

Other (OTH) AF: 0.00 AC: 0 AN: 46022

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 14

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.0080	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.082	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.90	T
PhyloP100		0.25
Sift4G	Benign	0.30	T
Polyphen		0.60	P
Vest4		0.31
MutPred		0.57		Gain of methylation at T207 (P = 0.0059)
MVP		0.055
ClinPred		0.34	T
GERP RS		1.8
Varity_R		0.10
gMVP		0.41
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: rs1331876224; hg19: chr10-47756706;