7-32559226-C-T

Position:

• chr7-32559226-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015060.3(AVL9):​c.977C>T​(p.Ser326Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 5.72

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2808244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AVL9	NM_015060.3	c.977C>T	p.Ser326Phe	missense_variant	10/16	ENST00000318709.9	NP_055875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AVL9	ENST00000318709.9	c.977C>T	p.Ser326Phe	missense_variant	10/16	2	NM_015060.3	ENSP00000315568.4
AVL9	ENST00000409301.5	c.977C>T	p.Ser326Phe	missense_variant	10/15	5		ENSP00000387011.1
AVL9	ENST00000446718.1	c.770C>T	p.Ser257Phe	missense_variant	9/13	5		ENSP00000395134.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Apr 08, 2024

The c.977C>T (p.S326F) alteration is located in exon 10 (coding exon 10) of the AVL9 gene. This alteration results from a C to T substitution at nucleotide position 977, causing the serine (S) at amino acid position 326 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	0.19
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;.;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Pathogenic	3.1	M;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.2	N;N;.;N
REVEL	Benign	0.18
Sift	Uncertain	0.0020	D;D;.;D
Sift4G	Uncertain	0.0090	D;D;.;D
Polyphen		0.98	D;.;.;.
Vest4		0.45
MutPred		0.21		Loss of phosphorylation at S326 (P = 0.005);Loss of phosphorylation at S326 (P = 0.005);Loss of phosphorylation at S326 (P = 0.005);.;
MVP		0.80
MPC		0.74
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.35
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-32598838;