rs878854744

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-155833459-C-G
• chr3-155833459-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_004733.4(SLC33A1):​c.1266+9G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC33A1 NM_004733.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-155833459-C-G is Benign according to our data. Variant chr3-155833459-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 240071.Status of the report is criteria_provided_single_submitter, 1 stars.

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>C		intron	N/A	NP_004724.1	O00400
	SLC33A1	NM_001190992.2		c.1266+9G>C		intron	N/A	NP_001177921.1	O00400
	SLC33A1	NM_001363883.1		c.960+398G>C		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>C		intron	N/A	ENSP00000496241.1	O00400
	SLC33A1	ENST00000359479.7	TSL:1	c.1266+9G>C		intron	N/A	ENSP00000352456.3	O00400
	ENSG00000284952	ENST00000643876.1		n.*588+9G>C		intron	N/A	ENSP00000495323.1	A0A2R8Y6H1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 16

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.1
DANN	Benign	0.66
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;