3-161369946-A-T

Variant names:

• chr3-161369946-A-T
• rs463928
• NM_001040100.2:c.-126+1489T>A

Variant summary

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

The NM_001040100.2(SPTSSB):​c.-126+1489T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 152,098 control chromosomes in the GnomAD database, including 29,188 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 0.60 (29188 hom., cov: 33)
• Consequence: SPTSSB NM_001040100.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 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.-126+1489T>A		intron	N/A	NP_001035189.1	Q8NFR3
	SPTSSB	NM_001320679.2		c.-265+1489T>A		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.-126+1489T>A		intron	N/A	ENSP00000480827.1	Q8NFR3
	SPTSSB	ENST00000359175.9	TSL:1	c.-126+1489T>A		intron	N/A	ENSP00000352097.4	Q8NFR3
	SPTSSB	ENST00000497137.1	TSL:3	c.-265+1489T>A		intron	N/A	ENSP00000420115.1	Q8NFR3

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91813 AN: 151980 Hom.: 29137 Cov.: 33

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.604 AC: 91922 AN: 152098 Hom.: 29188 Cov.: 33 AF XY: 0.609 AC XY: 45313 AN XY: 74346

African (AFR) AF: 0.738 AC: 30610 AN: 41488

American (AMR) AF: 0.668 AC: 10215 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1982 AN: 3466

East Asian (EAS) AF: 0.965 AC: 4988 AN: 5170

South Asian (SAS) AF: 0.727 AC: 3502 AN: 4820

European-Finnish (FIN) AF: 0.496 AC: 5241 AN: 10564

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33768 AN: 67992

Other (OTH) AF: 0.576 AC: 1216 AN: 2110

Alfa AF: 0.559 Hom.: 3048

Bravo AF: 0.621

Asia WGS AF: 0.834 AC: 2900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.1
DANN	Benign	0.76
PhyloP100		0.37
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: rs463928; hg19: chr3-161087734;