chr7-32544760-A-T

Position:

• chr7-32544760-A-T

Variant summary

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

The NM_015060.3(AVL9):​c.281A>T​(p.Tyr94Phe) variant causes a missense change involving the alteration of a conserved nucleotide. 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: AVL9 NM_015060.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.88

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 (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
AVL9	NM_015060.3	c.281A>T	p.Tyr94Phe	missense_variant	3/16	ENST00000318709.9	NP_055875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AVL9	ENST00000318709.9	c.281A>T	p.Tyr94Phe	missense_variant	3/16	2	NM_015060.3	ENSP00000315568.4
AVL9	ENST00000409301.5	c.281A>T	p.Tyr94Phe	missense_variant	3/15	5		ENSP00000387011.1
AVL9	ENST00000446718.1	c.74A>T	p.Tyr25Phe	missense_variant	2/13	5		ENSP00000395134.1
AVL9	ENST00000485228.1	n.378-6574A>T		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jul 30, 2023

The c.281A>T (p.Y94F) alteration is located in exon 3 (coding exon 3) of the AVL9 gene. This alteration results from a A to T substitution at nucleotide position 281, causing the tyrosine (Y) at amino acid position 94 to be replaced by a phenylalanine (F). 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	0.21
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.97
DEOGEN2	Benign	0.050	T;T;.;T
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.0078	T
MetaRNN	Uncertain	0.65	D;D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.9	L;.;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.1	N;N;.;N
REVEL	Uncertain	0.35
Sift	Benign	0.32	T;T;.;T
Sift4G	Benign	0.20	T;T;.;T
Polyphen		1.0	D;.;.;.
Vest4		0.61
MutPred		0.70		Gain of MoRF binding (P = 0.2143);Gain of MoRF binding (P = 0.2143);Gain of MoRF binding (P = 0.2143);.;
MVP		0.45
MPC		0.25
ClinPred		0.87	D
GERP RS		5.9
Varity_R		0.26
gMVP		0.35

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: chr7-32584372;