Variant 7-32554594-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015060.3(AVL9):c.607A>G(p.Lys203Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000123 in 1,548,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

AVL9
NM_015060.3 missense, splice_region

Scores

Splicing: ADA: 0.2164

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.32

Variant links:

Genes affected

AVL9 (HGNC:28994): (AVL9 cell migration associated) Involved in cell migration. Located in recycling endosome. [provided by Alliance of Genome Resources, Apr 2022]

AVL9 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.925

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AVL9	NM_015060.3 linkuse as main transcript	c.607A>G	p.Lys203Glu	missense_variant, splice_region_variant	8/16	ENST00000318709.9	NP_055875.1	Q8NBF6-1A0A024RA36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AVL9	ENST00000318709.9 linkuse as main transcript	c.607A>G	p.Lys203Glu	missense_variant, splice_region_variant	8/16	2	NM_015060.3	ENSP00000315568.4	Q8NBF6-1
AVL9	ENST00000409301.5 linkuse as main transcript	c.607A>G	p.Lys203Glu	missense_variant, splice_region_variant	8/15	5		ENSP00000387011.1	B8ZZW5
AVL9	ENST00000446718.1 linkuse as main transcript	c.400A>G	p.Lys134Glu	missense_variant, splice_region_variant	7/13	5		ENSP00000395134.1	H7C0I1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000129

AC:

AN:

1396216

Hom.:

Cov.:

AF XY:

0.0000202

AC XY:

AN XY:

693580

show subpopulations

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:

0.0000168

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000189

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

Jan 08, 2024

The c.607A>G (p.K203E) alteration is located in exon 8 (coding exon 8) of the AVL9 gene. This alteration results from a A to G substitution at nucleotide position 607, causing the lysine (K) at amino acid position 203 to be replaced by a glutamic acid (E). 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

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;T;.;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.92

D;D;D;D

MetaSVM

Uncertain

-0.21

MutationAssessor

Pathogenic

3.4

M;.;.;.

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.4

N;D;.;D

REVEL

Uncertain

0.58

Sift

Uncertain

0.0040

D;D;.;D

Sift4G

Uncertain

0.011

D;D;.;D

Polyphen

1.0

D;.;.;.

Vest4

0.91

MutPred

0.85

Loss of methylation at K203 (P = 0.0134);Loss of methylation at K203 (P = 0.0134);Loss of methylation at K203 (P = 0.0134);.;

MVP

0.81

MPC

0.86

ClinPred

0.98

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.57

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.22

dbscSNV1_RF

Benign

0.43

SpliceAI score (max)

0.070

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