rs149522913

Variant names:

• chr3-155829681-T-C
• rs149522913
• NM_004733.4:c.1482+7A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-155829681-T-C
• chr3-155829681-T-G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_004733.4(SLC33A1):​c.1482+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000779 in 1,593,736 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0043 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00040 (7 hom.)
• Consequence: SLC33A1 NM_004733.4 splice_region, intron
• Scores: Splicing: ADA: 0.00009264
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.251
• Publications: 1 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet, PanelApp Australia
• hereditary spastic paraplegia 42

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Illumina, PanelApp Australia, Orphanet

ENSG00000284952 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 3-155829681-T-C is Benign according to our data. Variant chr3-155829681-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 416702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 11 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004733.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC33A1	NM_004733.4	MANE Select	c.1482+7A>G		splice_region intron	N/A	NP_004724.1	O00400
	SLC33A1	NM_001190992.2		c.1482+7A>G		splice_region intron	N/A	NP_001177921.1	O00400
	SLC33A1	NM_001363883.1		c.1176+7A>G		splice_region intron	N/A	NP_001350812.1	A0A2R8YF57

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC33A1	ENST00000643144.2	MANE Select	c.1482+7A>G		splice_region intron	N/A	ENSP00000496241.1	O00400
	SLC33A1	ENST00000359479.7	TSL:1	c.1482+7A>G		splice_region intron	N/A	ENSP00000352456.3	O00400
	ENSG00000284952	ENST00000643876.1		n.*804+7A>G		splice_region intron	N/A	ENSP00000495323.1	A0A2R8Y6H1

Frequencies

GnomAD3 genomes AF: 0.00431 AC: 656 AN: 152186 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00120 AC: 301 AN: 251394 AF XY: 0.000861

Gnomad AFR exome AF: 0.0158

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000402 AC: 579 AN: 1441432 Hom.: 7 Cov.: 27 AF XY: 0.000334 AC XY: 240 AN XY: 718596

African (AFR) AF: 0.0141 AC: 467 AN: 33062

American (AMR) AF: 0.00125 AC: 56 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26014

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.0000699 AC: 6 AN: 85842

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5734

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1093404

Other (OTH) AF: 0.000787 AC: 47 AN: 59700

GnomAD4 genome AF: 0.00435 AC: 662 AN: 152304 Hom.: 11 Cov.: 32 AF XY: 0.00398 AC XY: 296 AN XY: 74464

African (AFR) AF: 0.0150 AC: 622 AN: 41562

American (AMR) AF: 0.00183 AC: 28 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00143 Hom.: 1

Bravo AF: 0.00482

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Hereditary spastic paraplegia (1)
-	-	1	Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.6
DANN	Benign	0.78
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000093
dbscSNV1_RF	Benign	0.0040
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: rs149522913; hg19: chr3-155547470;