3-155826591-T-C

Variant names:

• chr3-155826591-T-C
• rs10513483
• NM_004733.4:c.*1619A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004733.4(SLC33A1):​c.*1619A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 152,010 control chromosomes in the GnomAD database, including 1,676 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.099 (1676 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SLC33A1 NM_004733.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.870
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC33A1	NM_004733.4	c.*1619A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000643144.2	NP_004724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC33A1	ENST00000643144.2	c.*1619A>G		3_prime_UTR_variant	Exon 6 of 6		NM_004733.4	ENSP00000496241.1
ENSG00000284952	ENST00000643876.1	n.*1000+1591A>G		intron_variant	Intron 6 of 9			ENSP00000495323.1

Frequencies

GnomAD3 genomes AF: 0.0985 AC: 14963 AN: 151890 Hom.: 1674 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0119

Gnomad OTH AF: 0.0865

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0986 AC: 14994 AN: 152010 Hom.: 1676 Cov.: 32 AF XY: 0.0983 AC XY: 7303 AN XY: 74324

African (AFR) AF: 0.256 AC: 10612 AN: 41450

American (AMR) AF: 0.174 AC: 2648 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.106 AC: 544 AN: 5156

South Asian (SAS) AF: 0.0352 AC: 169 AN: 4798

European-Finnish (FIN) AF: 0.00226 AC: 24 AN: 10602

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0119 AC: 807 AN: 67974

Other (OTH) AF: 0.0847 AC: 179 AN: 2114

Alfa AF: 0.0443 Hom.: 738

Bravo AF: 0.119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.77
PhyloP100		-0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs10513483; hg19: chr3-155544380;