10-46390890-A-T

Position:

• chr10-46390890-A-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The ENST00000619162.5(ANXA8L1):​c.944A>T​(p.Tyr315Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 16)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANXA8L1 ENST00000619162.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.08

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31518185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA8L1	NM_001098845.3	c.944A>T	p.Tyr315Phe	missense_variant	12/12	ENST00000619162.5	NP_001092315.2
ANXA8L1	NM_001278924.2	c.791A>T	p.Tyr264Phe	missense_variant	9/9		NP_001265853.1
ANXA8L1	NM_001278923.2	c.773A>T	p.Tyr258Phe	missense_variant	10/10		NP_001265852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA8L1	ENST00000619162.5	c.944A>T	p.Tyr315Phe	missense_variant	12/12	1	NM_001098845.3	ENSP00000480221	P1

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1276524 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 633216

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 16

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.944A>T (p.Y315F) alteration is located in exon 12 (coding exon 12) of the ANXA8L1 gene. This alteration results from a A to T substitution at nucleotide position 944, causing the tyrosine (Y) at amino acid position 315 to be replaced by a phenylalanine (F). 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	0.19
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;.;.;T;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.079
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.32	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;N;N;N
Sift4G	Benign	0.13	T;T;T;T;T
Polyphen		1.0, 0.96	.;.;D;D;D
Vest4		0.44
MutPred		0.62		.;.;.;Gain of methylation at K316 (P = 0.0304);.;
MVP		0.14
ClinPred		0.71	D
GERP RS		1.9
Varity_R		0.077
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr10-47762147;