4-168179259-A-T

Position:

• chr4-168179259-A-T

Variant summary

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

The ENST00000359299.8(ANXA10):​c.671A>T​(p.Asp224Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANXA10 ENST00000359299.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.69

Genes affected

ANXA10 (HGNC:534): (annexin A10) This gene encodes a member of the annexin family. Members of this calcium-dependent phospholipid-binding protein family play a role in the regulation of cellular growth and in signal transduction pathways. The function of this gene has not yet been determined. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA10	NM_007193.5	c.671A>T	p.Asp224Val	missense_variant	9/12	ENST00000359299.8	NP_009124.2
LOC105377524	XR_007058356.1	n.141-6981T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA10	ENST00000359299.8	c.671A>T	p.Asp224Val	missense_variant	9/12	1	NM_007193.5	ENSP00000352248	P1
ANXA10	ENST00000507278.5	n.334A>T		non_coding_transcript_exon_variant	4/7	1
	ENST00000654434.1	n.466-6981T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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

Sep 13, 2023

The c.671A>T (p.D224V) alteration is located in exon 9 (coding exon 9) of the ANXA10 gene. This alteration results from a A to T substitution at nucleotide position 671, causing the aspartic acid (D) at amino acid position 224 to be replaced by a valine (V). 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	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.12
Sift	Benign	0.091	T
Sift4G	Benign	0.13	T
Polyphen		0.52	P
Vest4		0.66
MutPred		0.47		Loss of disorder (P = 0.2162);
MVP		0.41
MPC		0.25
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.30
gMVP		0.63

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-169100410;