9-77221345-G-T

Variant names:

• chr9-77221345-G-T
• NM_033305.3:c.1150G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033305.3(VPS13A):​c.1150G>T​(p.Val384Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: VPS13A NM_033305.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

Genes affected

VPS13A (HGNC:1908): (vacuolar protein sorting 13 homolog A) The protein encoded by this gene may control steps in the cycling of proteins through the trans-Golgi network to endosomes, lysosomes and the plasma membrane. Mutations in this gene cause the autosomal recessive disorder, chorea-acanthocytosis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029864639).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13A	NM_033305.3	c.1150G>T	p.Val384Leu	missense_variant	Exon 13 of 72	ENST00000360280.8	NP_150648.2
VPS13A	NM_001018037.2	c.1150G>T	p.Val384Leu	missense_variant	Exon 13 of 71		NP_001018047.1
VPS13A	NM_015186.4	c.1150G>T	p.Val384Leu	missense_variant	Exon 13 of 69		NP_056001.1
VPS13A	NM_001018038.3	c.1150G>T	p.Val384Leu	missense_variant	Exon 13 of 69		NP_001018048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13A	ENST00000360280.8	c.1150G>T	p.Val384Leu	missense_variant	Exon 13 of 72	1	NM_033305.3	ENSP00000353422.3
VPS13A	ENST00000376636.7	c.1150G>T	p.Val384Leu	missense_variant	Exon 13 of 71	1		ENSP00000365823.3
VPS13A	ENST00000643348.1	c.1150G>T	p.Val384Leu	missense_variant	Exon 13 of 69			ENSP00000493592.1
VPS13A	ENST00000645632.1	c.1150G>T	p.Val384Leu	missense_variant	Exon 13 of 69			ENSP00000496361.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460410 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726494

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.5
DANN	Benign	0.90
DEOGEN2	Benign	0.14	.;.;T;.;.;.;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.57	.;T;.;.;T;T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.030	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;N;N;N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.24	N;N;N;N;.;.;.
REVEL	Benign	0.036
Sift	Benign	0.57	T;T;T;T;.;.;.
Sift4G	Benign	0.13	T;T;T;T;.;.;.
Polyphen		0.0	B;B;B;B;B;B;B
Vest4		0.13
MutPred		0.27		Gain of disorder (P = 0.1235);Gain of disorder (P = 0.1235);Gain of disorder (P = 0.1235);Gain of disorder (P = 0.1235);Gain of disorder (P = 0.1235);Gain of disorder (P = 0.1235);Gain of disorder (P = 0.1235);
MVP		0.11
MPC		0.13
ClinPred		0.027	T
GERP RS		0.83
Varity_R		0.039
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr9-79836261;