3-155841653-G-T

Variant names:

• chr3-155841653-G-T
• rs11927551
• NM_004733.4:c.963+779C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

SLC33A1 Gene-Disease associations (from GenCC):

• Huppke-Brendel syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• hereditary spastic paraplegia 42

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Illumina, Orphanet

ENSG00000284952 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004733.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC33A1	NM_004733.4	MANE Select	c.963+779C>A		intron	N/A	NP_004724.1
	SLC33A1	NM_001190992.2		c.963+779C>A		intron	N/A	NP_001177921.1
	SLC33A1	NM_001363883.1		c.776-7612C>A		intron	N/A	NP_001350812.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC33A1	ENST00000643144.2	MANE Select	c.963+779C>A		intron	N/A	ENSP00000496241.1
	SLC33A1	ENST00000359479.7	TSL:1	c.963+779C>A		intron	N/A	ENSP00000352456.3
	ENSG00000284952	ENST00000643876.1		n.*285+779C>A		intron	N/A	ENSP00000495323.1

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

African (AFR) AF: 0.669 AC: 27628 AN: 41288

American (AMR) AF: 0.411 AC: 6276 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1097 AN: 3468

East Asian (EAS) AF: 0.332 AC: 1716 AN: 5168

South Asian (SAS) AF: 0.457 AC: 2206 AN: 4826

European-Finnish (FIN) AF: 0.214 AC: 2248 AN: 10506

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19136 AN: 67916

Other (OTH) AF: 0.394 AC: 832 AN: 2110

Alfa AF: 0.273 Hom.: 1120

Bravo AF: 0.428

Asia WGS AF: 0.389 AC: 1352 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.71
PhyloP100		0.019
Mutation Taster		=100/0	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: rs11927551; hg19: chr3-155559442;