Variant 7-32548860-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015060.3(AVL9):c.314G>A(p.Arg105Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,421,272 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

AVL9
NM_015060.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.65

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:

AVL9 (HGNC:):

AVL9 links:

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ACMG classification

Classification made for transcript

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
AVL9	NM_015060.3 linkuse as main transcript	c.314G>A	p.Arg105Lys	missense_variant	4/16	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.314G>A	p.Arg105Lys	missense_variant	4/16	2	NM_015060.3	ENSP00000315568.4	Q8NBF6-1
AVL9	ENST00000409301.5 linkuse as main transcript	c.314G>A	p.Arg105Lys	missense_variant	4/15	5		ENSP00000387011.1	B8ZZW5
AVL9	ENST00000446718.1 linkuse as main transcript	c.107G>A	p.Arg36Lys	missense_variant	3/13	5		ENSP00000395134.1	H7C0I1
AVL9	ENST00000485228.1 linkuse as main transcript	n.378-2474G>A		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000876

AC:

AN:

228246

Hom.:

AF XY:

0.00000806

AC XY:

AN XY:

124064

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000724

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000211

AC:

AN:

1421272

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

705706

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000521

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:

9.14e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Aug 16, 2021

The c.314G>A (p.R105K) alteration is located in exon 4 (coding exon 4) of the AVL9 gene. This alteration results from a G to A substitution at nucleotide position 314, causing the arginine (R) at amino acid position 105 to be replaced by a lysine (K). 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

Uncertain

0.39

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

T;T;.;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.62

D;D;D;D

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

L;.;.;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.68

N;N;.;N

REVEL

Benign

0.18

Sift

Benign

0.28

T;T;.;T

Sift4G

Benign

0.49

T;T;.;T

Polyphen

0.87

P;.;.;.

Vest4

0.50

MutPred

0.74

Gain of methylation at R105 (P = 0.0201);Gain of methylation at R105 (P = 0.0201);Gain of methylation at R105 (P = 0.0201);.;

MVP

0.73

MPC

0.41

ClinPred

0.47

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.50

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