9-77177522-G-C

Variant names:

• chr9-77177522-G-C
• rs12349389
• ENST00000376636.7:c.-183G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000376636.7(VPS13A):​c.-183G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 599,262 control chromosomes in the GnomAD database, including 3,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (828 hom., cov: 33)
  • Exomes 𝑓: 0.097 (2317 hom.)
• Consequence: VPS13A ENST00000376636.7 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.100
• Publications: 5 publications found

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]

VPS13A-AS1 (HGNC:44167): (VPS13A antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 9-77177522-G-C is Benign according to our data. Variant chr9-77177522-G-C is described in ClinVar as Benign. ClinVar VariationId is 367337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000376636.7. 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
	VPS13A-AS1	NR_026668.2		n.291+105C>G		intron	N/A
	VPS13A	NM_033305.3	MANE Select	c.-183G>C		upstream_gene	N/A	NP_150648.2	Q96RL7-1
	VPS13A	NM_001018037.2		c.-183G>C		upstream_gene	N/A	NP_001018047.1	Q96RL7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13A	ENST00000376636.7	TSL:1	c.-183G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 71	ENSP00000365823.3	Q96RL7-3
	VPS13A	ENST00000376636.7	TSL:1	c.-183G>C		5_prime_UTR	Exon 1 of 71	ENSP00000365823.3	Q96RL7-3
	VPS13A-AS1	ENST00000644612.2		n.575+105C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15592 AN: 152060 Hom.: 828 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0745

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.0750

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0947

GnomAD4 exome AF: 0.0966 AC: 43192 AN: 447084 Hom.: 2317 Cov.: 5 AF XY: 0.0961 AC XY: 23026 AN XY: 239622

African (AFR) AF: 0.111 AC: 1308 AN: 11734

American (AMR) AF: 0.0522 AC: 1261 AN: 24178

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 1429 AN: 13588

East Asian (EAS) AF: 0.0346 AC: 962 AN: 27766

South Asian (SAS) AF: 0.0802 AC: 4036 AN: 50320

European-Finnish (FIN) AF: 0.123 AC: 3342 AN: 27220

Middle Eastern (MID) AF: 0.111 AC: 214 AN: 1924

European-Non Finnish (NFE) AF: 0.107 AC: 28287 AN: 265538

Other (OTH) AF: 0.0948 AC: 2353 AN: 24816

GnomAD4 genome AF: 0.103 AC: 15606 AN: 152178 Hom.: 828 Cov.: 33 AF XY: 0.102 AC XY: 7570 AN XY: 74420

African (AFR) AF: 0.111 AC: 4595 AN: 41530

American (AMR) AF: 0.0745 AC: 1140 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 393 AN: 3470

East Asian (EAS) AF: 0.0361 AC: 186 AN: 5156

South Asian (SAS) AF: 0.0751 AC: 362 AN: 4820

European-Finnish (FIN) AF: 0.124 AC: 1317 AN: 10614

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.108 AC: 7319 AN: 67968

Other (OTH) AF: 0.0938 AC: 198 AN: 2112

Alfa AF: 0.0342 Hom.: 29

Bravo AF: 0.0992

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Chorea-acanthocytosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.1
DANN	Benign	0.76
PhyloP100		-0.10
PromoterAI		-0.18	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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: rs12349389; hg19: chr9-79792438;