Variant 4-168177930-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000359299.8(ANXA10):c.575A>C(p.Lys192Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

ANXA10
ENST00000359299.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.96

Variant links:

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]

ANXA10 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.781

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA10	NM_007193.5 linkuse as main transcript	c.575A>C	p.Lys192Thr	missense_variant	8/12	ENST00000359299.8	NP_009124.2
LOC105377524	XR_007058356.1 linkuse as main transcript	n.141-5652T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ANXA10	ENST00000359299.8 linkuse as main transcript	c.575A>C	p.Lys192Thr	missense_variant	8/12	1	NM_007193.5	ENSP00000352248	P1
ANXA10	ENST00000507278.5 linkuse as main transcript	n.238A>C		non_coding_transcript_exon_variant	3/7	1
	ENST00000654434.1 linkuse as main transcript	n.466-5652T>G		intron_variant, non_coding_transcript_variant
ANXA10	ENST00000503003.1 linkuse as main transcript	n.181A>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461458

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

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:

0.0000994

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 21, 2021

The c.575A>C (p.K192T) alteration is located in exon 8 (coding exon 8) of the ANXA10 gene. This alteration results from a A to C substitution at nucleotide position 575, causing the lysine (K) at amino acid position 192 to be replaced by a threonine (T). 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

0.31

BayesDel_addAF

Benign

0.0096

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.012

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-1.2

MutationAssessor

Benign

0.76

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.9

REVEL

Benign

0.27

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.023

Polyphen

1.0

Vest4

0.63

MutPred

0.66

Loss of ubiquitination at K192 (P = 0.0167);

MVP

0.26

MPC

0.34

ClinPred

0.91

GERP RS

5.7

Varity_R

0.31

gMVP

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over