NM_033305.3:c.-148C>T

Variant names:

• chr9-77177557-C-T
• rs555695029
• NM_033305.3:c.-148C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_033305.3(VPS13A):​c.-148C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 721,756 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (3 hom.)
• Consequence: VPS13A NM_033305.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.286
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00183 (278/152270) while in subpopulation NFE AF = 0.00296 (201/68002). AF 95% confidence interval is 0.00262. There are 2 homozygotes in GnomAd4. There are 130 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033305.3. 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
	VPS13A	NM_033305.3	MANE Select	c.-148C>T		5_prime_UTR	Exon 1 of 72	NP_150648.2	Q96RL7-1
	VPS13A	NM_001018037.2		c.-148C>T		5_prime_UTR	Exon 1 of 71	NP_001018047.1	Q96RL7-3
	VPS13A	NM_015186.4		c.-148C>T		5_prime_UTR	Exon 1 of 69	NP_056001.1	Q96RL7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13A	ENST00000360280.8	TSL:1 MANE Select	c.-148C>T		5_prime_UTR	Exon 1 of 72	ENSP00000353422.3	Q96RL7-1
	VPS13A	ENST00000376636.7	TSL:1	c.-148C>T		5_prime_UTR	Exon 1 of 71	ENSP00000365823.3	Q96RL7-3
	VPS13A	ENST00000643348.1		c.-148C>T		5_prime_UTR	Exon 1 of 69	ENSP00000493592.1	Q96RL7-2

Frequencies

GnomAD3 genomes AF: 0.00183 AC: 278 AN: 152152 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00296

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.00229 AC: 1304 AN: 569486 Hom.: 3 Cov.: 7 AF XY: 0.00211 AC XY: 645 AN XY: 305770

African (AFR) AF: 0.000703 AC: 11 AN: 15638

American (AMR) AF: 0.000926 AC: 31 AN: 33462

Ashkenazi Jewish (ASJ) AF: 0.000163 AC: 3 AN: 18452

East Asian (EAS) AF: 0.00 AC: 0 AN: 30780

South Asian (SAS) AF: 0.000232 AC: 14 AN: 60338

European-Finnish (FIN) AF: 0.00295 AC: 94 AN: 31832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2502

European-Non Finnish (NFE) AF: 0.00316 AC: 1096 AN: 346378

Other (OTH) AF: 0.00183 AC: 55 AN: 30104

GnomAD4 genome AF: 0.00183 AC: 278 AN: 152270 Hom.: 2 Cov.: 33 AF XY: 0.00175 AC XY: 130 AN XY: 74452

African (AFR) AF: 0.000794 AC: 33 AN: 41572

American (AMR) AF: 0.00137 AC: 21 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00296 AC: 201 AN: 68002

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.000744 Hom.: 1

Bravo AF: 0.00176

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Chorea-acanthocytosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		0.29
PromoterAI		-0.024	Neutral
Mutation Taster		=297/3	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: rs555695029; hg19: chr9-79792473;