3-155828030-C-CA

Position:

• chr3-155828030-C-CA

Variant summary

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

The NM_004733.4(SLC33A1):​c.*179dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0462 in 479,172 control chromosomes in the GnomAD database, including 525 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.056 (430 hom., cov: 32)
  • Exomes 𝑓: 0.042 (95 hom.)
• Consequence: SLC33A1 NM_004733.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.424

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]

ENSG00000284952 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-155828030-C-CA is Benign according to our data. Variant chr3-155828030-C-CA is described in ClinVar as [Benign]. Clinvar id is 1293131.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC33A1	NM_004733.4	c.*179dupT		3_prime_UTR_variant	6/6	ENST00000643144.2	NP_004724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC33A1	ENST00000643144	c.*179dupT		3_prime_UTR_variant	6/6		NM_004733.4	ENSP00000496241.1
ENSG00000284952	ENST00000643876.1	n.*1000+151dupT		intron_variant				ENSP00000495323.1

Frequencies

GnomAD3 genomes AF: 0.0555 AC: 8094 AN: 145806 Hom.: 427 Cov.: 32

Gnomad AFR AF: 0.0987

Gnomad AMI AF: 0.00671

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.00148

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.00347

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.0547

GnomAD4 exome AF: 0.0421 AC: 14032 AN: 333270 Hom.: 95 Cov.: 4 AF XY: 0.0421 AC XY: 7390 AN XY: 175584

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.182

Gnomad4 ASJ exome AF: 0.0152

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.0483

Gnomad4 FIN exome AF: 0.0128

Gnomad4 NFE exome AF: 0.0267

Gnomad4 OTH exome AF: 0.0451

GnomAD4 genome AF: 0.0556 AC: 8114 AN: 145902 Hom.: 430 Cov.: 32 AF XY: 0.0587 AC XY: 4157 AN XY: 70842

Gnomad4 AFR AF: 0.0988

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.00148

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.0361

Gnomad4 FIN AF: 0.00347

Gnomad4 NFE AF: 0.0143

Gnomad4 OTH AF: 0.0531

Bravo AF: 0.0664

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

Aug 15, 2019

- -

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: rs201290926; hg19: chr3-155545819;