Variant 7-32543196-T-C 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.149T>C(p.Leu50Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

AVL9
NM_015060.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.96

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.149T>C	p.Leu50Ser	missense_variant	2/16	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.149T>C	p.Leu50Ser	missense_variant	2/16	2	NM_015060.3	ENSP00000315568.4	Q8NBF6-1
AVL9	ENST00000409301.5 linkuse as main transcript	c.149T>C	p.Leu50Ser	missense_variant	2/15	5		ENSP00000387011.1	B8ZZW5
AVL9	ENST00000485228.1 linkuse as main transcript	n.378-8138T>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Feb 03, 2023

The c.149T>C (p.L50S) alteration is located in exon 2 (coding exon 2) of the AVL9 gene. This alteration results from a T to C substitution at nucleotide position 149, causing the leucine (L) at amino acid position 50 to be replaced by a serine (S). 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

0.81

BayesDel_addAF

Uncertain

0.049

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;T;.

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.55

D;D;D

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.2

M;.;.

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.8

D;D;.

REVEL

Benign

0.26

Sift

Uncertain

0.0060

D;D;.

Sift4G

Uncertain

0.0080

D;D;.

Polyphen

0.86

P;.;.

Vest4

0.70

MutPred

0.56

Loss of catalytic residue at L50 (P = 0.0058);Loss of catalytic residue at L50 (P = 0.0058);Loss of catalytic residue at L50 (P = 0.0058);

MVP

0.67

MPC

0.32

ClinPred

0.93

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.25

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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