rs200789237

chr3-155842548-C-Gchr3-155842548-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004733.4(SLC33A1):c.847G>C(p.Glu283Gln) variant causes a missense 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. 12/21 in silico tools predict a benign outcome for this variant. 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. E283K) 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: 2.17

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20608205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC33A1	NM_004733.4	c.847G>C	p.Glu283Gln	missense_variant	2/6	ENST00000643144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC33A1	ENST00000643144.2	c.847G>C	p.Glu283Gln	missense_variant	2/6		NM_004733.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;T;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	0.83	L;L;L;.
MutationTaster	Benign	0.59	N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.2	N;.;N;N
REVEL	Benign	0.24
Sift	Benign	0.20	T;.;T;T
Sift4G	Benign	0.18	T;.;T;T
Polyphen		0.79	P;P;P;.
Vest4		0.16
MutPred		0.38		Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);.;
MVP		0.79
MPC		0.42
ClinPred		0.54	D
GERP RS		5.5
Varity_R		0.068
gMVP		0.55

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: rs200789237; hg19: chr3-155560337;