rs144015992

Variant names:

• chr3-155829719-T-C
• rs144015992
• NM_004733.4:c.1451A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-155829719-T-C
• chr3-155829719-T-G

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.1451A>G​(p.Asn484Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. N484T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC33A1 NM_004733.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.878
• 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• hereditary spastic paraplegia 42

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Illumina, 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 (MetaRNN=0.05051908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC33A1	NM_004733.4	c.1451A>G	p.Asn484Ser	missense_variant	Exon 5 of 6	ENST00000643144.2	NP_004724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC33A1	ENST00000643144.2	c.1451A>G	p.Asn484Ser	missense_variant	Exon 5 of 6		NM_004733.4	ENSP00000496241.1
ENSG00000284952	ENST00000643876.1	n.*773A>G		non_coding_transcript_exon_variant	Exon 5 of 10			ENSP00000495323.1
ENSG00000284952	ENST00000643876.1	n.*773A>G		3_prime_UTR_variant	Exon 5 of 10			ENSP00000495323.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461758 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727178

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111904

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.058	T;T;T;.;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.0	.;.;T;T;T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.051	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.040	N;N;N;.;.
PhyloP100		0.88
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.16	N;.;N;.;N
REVEL	Benign	0.071
Sift	Benign	0.80	T;.;T;.;T
Sift4G	Benign	0.78	T;.;T;.;T
Vest4		0.18
ClinPred		0.14	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.025
gMVP		0.37
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs144015992; hg19: chr3-155547508;