3-155828040-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004733.4(SLC33A1):c.*169del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00753 in 577,750 control chromosomes in the GnomAD database, including 119 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (105 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (14 hom.)
• Consequence: SLC33A1 NM_004733.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.158

Genes affected

SLC33A1 (HGNC:95): (solute carrier family 33 member 1) The protein encoded by this gene is required for the formation of O-acetylated (Ac) gangliosides. The encoded protein is predicted to contain 6 to 10 transmembrane domains, and a leucine zipper motif in transmembrane domain III. Defects in this gene have been reported to cause spastic paraplegia autosomal dominant type 42 (SPG42) in one Chinese family, but not in similar patients of European descent. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-155828040-AT-A is Benign according to our data. Variant chr3-155828040-AT-A is described in ClinVar as [Benign]. Clinvar id is 1274993.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC33A1	NM_004733.4	c.*169del		3_prime_UTR_variant	6/6	ENST00000643144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC33A1	ENST00000643144.2	c.*169del		3_prime_UTR_variant	6/6		NM_004733.4	P1

Frequencies

GnomAD3 genomes AF: 0.0213 AC: 3237 AN: 152118 Hom.: 105 Cov.: 32

Gnomad AFR AF: 0.0744

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00669

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0167

GnomAD4 exome AF: 0.00259 AC: 1101 AN: 425514 Hom.: 14 Cov.: 5 AF XY: 0.00214 AC XY: 480 AN XY: 224186

Gnomad4 AFR exome AF: 0.0669

Gnomad4 AMR exome AF: 0.00544

Gnomad4 ASJ exome AF: 0.00109

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000309

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000319

Gnomad4 OTH exome AF: 0.00593

GnomAD4 genome AF: 0.0213 AC: 3247 AN: 152236 Hom.: 105 Cov.: 32 AF XY: 0.0206 AC XY: 1533 AN XY: 74454

Gnomad4 AFR AF: 0.0744

Gnomad4 AMR AF: 0.00668

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.0166

Asia WGS AF: 0.00376 AC: 13 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs139894444; hg19: chr3-155545829;