3-155833459-C-T

Variant names:

• chr3-155833459-C-T
• rs878854744
• NM_004733.4:c.1266+9G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004733.4(SLC33A1):​c.1266+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000882 in 1,134,370 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: SLC33A1 NM_004733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898
• Publications: 0 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet, PanelApp Australia
• hereditary spastic paraplegia 42

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

ENSG00000284952 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC33A1	NM_004733.4	MANE Select	c.1266+9G>A		intron	N/A	NP_004724.1	O00400
	SLC33A1	NM_001190992.2		c.1266+9G>A		intron	N/A	NP_001177921.1	O00400
	SLC33A1	NM_001363883.1		c.960+398G>A		intron	N/A	NP_001350812.1	A0A2R8YF57

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC33A1	ENST00000643144.2	MANE Select	c.1266+9G>A		intron	N/A	ENSP00000496241.1	O00400
	SLC33A1	ENST00000359479.7	TSL:1	c.1266+9G>A		intron	N/A	ENSP00000352456.3	O00400
	ENSG00000284952	ENST00000643876.1		n.*588+9G>A		intron	N/A	ENSP00000495323.1	A0A2R8Y6H1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.82e-7 AC: 1 AN: 1134370 Hom.: 0 Cov.: 16 AF XY: 0.00000172 AC XY: 1 AN XY: 580312

African (AFR) AF: 0.00 AC: 0 AN: 27104

American (AMR) AF: 0.00 AC: 0 AN: 44350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24052

East Asian (EAS) AF: 0.00 AC: 0 AN: 38224

South Asian (SAS) AF: 0.00 AC: 0 AN: 79736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5136

European-Non Finnish (NFE) AF: 0.00000123 AC: 1 AN: 813048

Other (OTH) AF: 0.00 AC: 0 AN: 49454

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.6
DANN	Benign	0.61
PhyloP100		-0.90

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: rs878854744; hg19: chr3-155551248;