NM_004733.4:c.1450_1452delAACinsTCA

Variant names:

• chr3-155829718-GTT-TGA
• NM_004733.4:c.1450_1452delAACinsTCA
• SLC33A1 p.Asn484Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004733.4(SLC33A1):​c.1450_1452delAACinsTCA​(p.Asn484Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N484T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC33A1 NM_004733.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.25
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.1450_1452delAACinsTCA	p.Asn484Ser	missense	N/A	NP_004724.1	O00400
	SLC33A1	NM_001190992.2		c.1450_1452delAACinsTCA	p.Asn484Ser	missense	N/A	NP_001177921.1	O00400
	SLC33A1	NM_001363883.1		c.1144_1146delAACinsTCA	p.Asn382Ser	missense	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.1450_1452delAACinsTCA	p.Asn484Ser	missense	N/A	ENSP00000496241.1	O00400
	SLC33A1	ENST00000359479.7	TSL:1	c.1450_1452delAACinsTCA	p.Asn484Ser	missense	N/A	ENSP00000352456.3	O00400
	ENSG00000284952	ENST00000643876.1		n.*772_*774delAACinsTCA		non_coding_transcript_exon	Exon 5 of 10	ENSP00000495323.1	A0A2R8Y6H1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-155547507;