10-46382651-C-T

Variant names:

• chr10-46382651-C-T
• NM_001098845.3:c.280C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001098845.3(ANXA8L1):​c.280C>T​(p.Pro94Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 15)
• Consequence: ANXA8L1 NM_001098845.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.80

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24633554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA8L1	NM_001098845.3	c.280C>T	p.Pro94Ser	missense_variant	Exon 4 of 12	ENST00000619162.5	NP_001092315.2
ANXA8L1	NM_001278924.2	c.394C>T	p.Pro132Ser	missense_variant	Exon 4 of 9		NP_001265853.1
ANXA8L1	NM_001278923.2	c.280C>T	p.Pro94Ser	missense_variant	Exon 4 of 10		NP_001265852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA8L1	ENST00000619162.5	c.280C>T	p.Pro94Ser	missense_variant	Exon 4 of 12	1	NM_001098845.3	ENSP00000480221.1

Frequencies

GnomAD3 genomes Cov.: 15

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 15

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.280C>T (p.P94S) alteration is located in exon 4 (coding exon 4) of the ANXA8L2 gene. This alteration results from a C to T substitution at nucleotide position 280, causing the proline (P) at amino acid position 94 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;.;T;.
Eigen	Benign	-0.012
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.73	T;T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.25	T;T;T;T;T
MetaSVM	Benign	-0.88	T
Sift4G	Benign	0.12	T;T;T;T;T
Polyphen		1.0, 0.65	.;.;D;P;D
Vest4		0.53
MutPred		0.49		.;.;.;Loss of catalytic residue at P93 (P = 0.0107);Loss of catalytic residue at P93 (P = 0.0107);
MVP		0.27
ClinPred		0.74	D
GERP RS		1.8
Varity_R		0.12
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-47753910;