7-32583881-A-C

Variant names:

• chr7-32583881-A-C
• rs1329715787
• NM_015060.3:c.1921A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_015060.3(AVL9):​c.1921A>C​(p.Thr641Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AVL9 NM_015060.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.409
• Publications: 0 publications found

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]

DPY19L1P1 (HGNC:22395): (DPY19L1 pseudogene 1)

ENSG00000293957 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041190147).
• BP6: Variant 7-32583881-A-C is Benign according to our data. Variant chr7-32583881-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3132408.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015060.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AVL9	NM_015060.3	MANE Select	c.1921A>C	p.Thr641Pro	missense	Exon 16 of 16	NP_055875.1	Q8NBF6-1
	AVL9	NM_001410870.1		c.1867A>C	p.Thr623Pro	missense	Exon 15 of 15	NP_001397799.1	B8ZZW5
	DPY19L1P1	NR_036680.1		n.1435+2096T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AVL9	ENST00000318709.9	TSL:2 MANE Select	c.1921A>C	p.Thr641Pro	missense	Exon 16 of 16	ENSP00000315568.4	Q8NBF6-1
	AVL9	ENST00000884406.1		c.1933A>C	p.Thr645Pro	missense	Exon 16 of 16	ENSP00000554465.1
	AVL9	ENST00000884413.1		c.1885A>C	p.Thr629Pro	missense	Exon 16 of 16	ENSP00000554472.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000137 AC: 20 AN: 1461288 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11 AN XY: 726970

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111484

Other (OTH) AF: 0.0000166 AC: 1 AN: 60364

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.9
DANN	Benign	0.68
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.14	N
PhyloP100		0.41
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.083
Sift	Benign	0.22	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.052
MutPred		0.046		Loss of phosphorylation at T641 (P = 0.0129)
MVP		0.20
MPC		0.23
ClinPred		0.032	T
GERP RS		-1.3
Varity_R		0.048
gMVP		0.11
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs1329715787; hg19: chr7-32623493;