NM_001040100.2:c.-126+1631G>C

Variant names:

• chr3-161369804-C-G
• rs464766
• NM_001040100.2:c.-126+1631G>C

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+1631G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,834 control chromosomes in the GnomAD database, including 30,380 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 0.62 (30380 hom., cov: 30)
• Consequence: SPTSSB NM_001040100.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTSSB	NM_001040100.2	MANE Select	c.-126+1631G>C		intron	N/A	NP_001035189.1
	SPTSSB	NM_001320679.2		c.-265+1631G>C		intron	N/A	NP_001307608.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTSSB	ENST00000620149.2	TSL:6 MANE Select	c.-126+1631G>C		intron	N/A	ENSP00000480827.1
	SPTSSB	ENST00000359175.9	TSL:1	c.-126+1631G>C		intron	N/A	ENSP00000352097.4
	SPTSSB	ENST00000497137.1	TSL:3	c.-265+1631G>C		intron	N/A	ENSP00000420115.1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93767 AN: 151716 Hom.: 30330 Cov.: 30

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.618 AC: 93874 AN: 151834 Hom.: 30380 Cov.: 30 AF XY: 0.623 AC XY: 46187 AN XY: 74168

African (AFR) AF: 0.756 AC: 31276 AN: 41392

American (AMR) AF: 0.683 AC: 10435 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2049 AN: 3468

East Asian (EAS) AF: 0.966 AC: 4983 AN: 5160

South Asian (SAS) AF: 0.741 AC: 3562 AN: 4808

European-Finnish (FIN) AF: 0.499 AC: 5235 AN: 10490

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

European-Non Finnish (NFE) AF: 0.508 AC: 34503 AN: 67932

Other (OTH) AF: 0.593 AC: 1251 AN: 2108

Alfa AF: 0.570 Hom.: 3169

Bravo AF: 0.636

Asia WGS AF: 0.847 AC: 2944 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	1.4
DANN	Benign	0.57
PhyloP100		-0.066
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: rs464766; hg19: chr3-161087592;