3-155841653-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004733.4(SLC33A1):c.963+779C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,744 control chromosomes in the GnomAD database, including 14,696 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (14696 hom., cov: 32)
• Consequence: SLC33A1 NM_004733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC33A1	NM_004733.4	c.963+779C>A		intron_variant		ENST00000643144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC33A1	ENST00000643144.2	c.963+779C>A		intron_variant			NM_004733.4	P1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61366 AN: 151626 Hom.: 14668 Cov.: 32

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.398

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.405 AC: 61450 AN: 151744 Hom.: 14696 Cov.: 32 AF XY: 0.403 AC XY: 29925 AN XY: 74168

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.394

Alfa AF: 0.256 Hom.: 931

Bravo AF: 0.428

Asia WGS AF: 0.389 AC: 1352 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.1
Dann	Benign	0.71

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: rs11927551; hg19: chr3-155559442;