rs3804769

Positions:

• chr3-155853486-T-A
• chr3-155853486-T-C

Variant summary

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

The NM_004733.4(SLC33A1):​c.512A>T​(p.Asp171Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. D171G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC33A1 NM_004733.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.63

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC33A1	NM_004733.4	c.512A>T	p.Asp171Val	missense_variant	1/6	ENST00000643144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC33A1	ENST00000643144.2	c.512A>T	p.Asp171Val	missense_variant	1/6		NM_004733.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.097	T;T;T;.
Eigen	Benign	-0.056
Eigen_PC	Benign	0.042
FATHMM_MKL	Uncertain	0.83	D
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.0	N;N;N;.
MutationTaster	Benign	0.00016	P;P
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.4	N;.;N;.
REVEL	Benign	0.13
Sift	Benign	0.071	T;.;T;.
Sift4G	Benign	0.23	T;.;T;.
Polyphen		0.010	B;B;B;.
Vest4		0.20
MutPred		0.30		Loss of disorder (P = 0.0133);Loss of disorder (P = 0.0133);Loss of disorder (P = 0.0133);Loss of disorder (P = 0.0133);
MVP		0.83
MPC		1.5
ClinPred		0.79	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.080
gMVP		0.61

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: rs3804769; hg19: chr3-155571275;