3-155826533-GTTTT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004733.4(SLC33A1):c.*1673_*1676del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0849 in 151,928 control chromosomes in the GnomAD database, including 709 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.085 (709 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: SLC33A1 NM_004733.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.369

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 3-155826533-GTTTT-G is Benign according to our data. Variant chr3-155826533-GTTTT-G is described in ClinVar as [Likely_benign]. Clinvar id is 343855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC33A1	NM_004733.4	c.*1673_*1676del		3_prime_UTR_variant	6/6	ENST00000643144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC33A1	ENST00000643144.2	c.*1673_*1676del		3_prime_UTR_variant	6/6		NM_004733.4	P1
SLC33A1	ENST00000359479.7	c.*311_*314del		3_prime_UTR_variant	7/7	1		P1
SLC33A1	ENST00000468581.2	c.*2127_*2130del		3_prime_UTR_variant, NMD_transcript_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 12903 AN: 151810 Hom.: 710 Cov.: 31

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0743

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0931

Gnomad FIN AF: 0.0951

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0947

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0849 AC: 12893 AN: 151928 Hom.: 709 Cov.: 31 AF XY: 0.0814 AC XY: 6047 AN XY: 74246

Gnomad4 AFR AF: 0.0237

Gnomad4 AMR AF: 0.0742

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0931

Gnomad4 FIN AF: 0.0951

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.0933

Alfa AF: 0.0477 Hom.: 45

Bravo AF: 0.0801

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spastic paraplegia, autosomal dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs143606890; hg19: chr3-155544322;