3-161364193-T-A

Variant names:

• chr3-161364193-T-A
• rs336583
• NM_001040100.2:c.-125-4299A>T

Variant summary

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

The NM_001040100.2(SPTSSB):​c.-125-4299A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 151,820 control chromosomes in the GnomAD database, including 33,873 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 0.65 (33873 hom., cov: 30)
• Consequence: SPTSSB NM_001040100.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 6 publications found

Genes affected

SPTSSB (HGNC:24045): (serine palmitoyltransferase small subunit B) Serine palmitoyltransferase (SPT; EC 2.3.1.50) catalyzes the first committed and rate-limiting step in sphingolipid biosynthesis. SSSPTB is a small SPT subunit that stimulates SPT activity and confers acyl-CoA preference to the SPT catalytic heterodimer of SPTLC1 (MIM 605712) and either SPTLC2 (MIM 605713) or SPTLC3 (MIM 611120) (Han et al., 2009 [PubMed 19416851]).[supplied by OMIM, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040100.2. 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
	SPTSSB	NM_001040100.2	MANE Select	c.-125-4299A>T		intron	N/A	NP_001035189.1	Q8NFR3
	SPTSSB	NM_001320679.2		c.-264-4299A>T		intron	N/A	NP_001307608.1	Q8NFR3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTSSB	ENST00000620149.2	TSL:6 MANE Select	c.-125-4299A>T		intron	N/A	ENSP00000480827.1	Q8NFR3
	SPTSSB	ENST00000359175.9	TSL:1	c.-125-4299A>T		intron	N/A	ENSP00000352097.4	Q8NFR3
	SPTSSB	ENST00000497137.1	TSL:3	c.-264-4299A>T		intron	N/A	ENSP00000420115.1	Q8NFR3

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98115 AN: 151702 Hom.: 33812 Cov.: 30

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.647 AC: 98235 AN: 151820 Hom.: 33873 Cov.: 30 AF XY: 0.651 AC XY: 48271 AN XY: 74194

African (AFR) AF: 0.853 AC: 35369 AN: 41440

American (AMR) AF: 0.696 AC: 10605 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2068 AN: 3468

East Asian (EAS) AF: 0.966 AC: 4984 AN: 5158

South Asian (SAS) AF: 0.742 AC: 3563 AN: 4802

European-Finnish (FIN) AF: 0.498 AC: 5245 AN: 10524

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34514 AN: 67880

Other (OTH) AF: 0.619 AC: 1303 AN: 2106

Alfa AF: 0.446 Hom.: 1236

Bravo AF: 0.670

Asia WGS AF: 0.855 AC: 2971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.29
PhyloP100		-0.077
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: rs336583; hg19: chr3-161081981;