rs2144134

Variant names:

• chr20-13167505-C-G
• rs2144134
• NM_018327.4:c.*2638C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018327.4(SPTLC3):​c.*2638C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,938 control chromosomes in the GnomAD database, including 16,816 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 0.47 (16816 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPTLC3 NM_018327.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227

Genes affected

SPTLC3 (HGNC:16253): (serine palmitoyltransferase long chain base subunit 3) This gene encodes a subunit of the serine palmitoyltransferase complex which catalyzes the rate-limiting step in sphingolipid biosynthesis. This subunit metabolizes lauroyl- and myristoyl-CoA and generates C14 and C16-sphingoid bases. [provided by RefSeq, Mar 2017]

TASP1 (HGNC:15859): (taspase 1) This gene encodes an endopeptidase that cleaves specific substrates following aspartate residues. The encoded protein undergoes posttranslational autoproteolytic processing to generate alpha and beta subunits, which reassemble into the active alpha2-beta2 heterotetramer. It is required to cleave MLL, a protein required for the maintenance of HOX gene expression, and TFIIA, a basal transcription factor. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTLC3	NM_018327.4	c.*2638C>G		3_prime_UTR_variant	Exon 12 of 12	ENST00000399002.7	NP_060797.2
SPTLC3	NM_001349945.2	c.*2638C>G		3_prime_UTR_variant	Exon 13 of 13		NP_001336874.1
SPTLC3	XM_011529280.2	c.*2638C>G		3_prime_UTR_variant	Exon 9 of 9		XP_011527582.1
TASP1	XR_001754319.3	n.1370-62248G>C		intron_variant	Intron 14 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTLC3	ENST00000399002.7	c.*2638C>G		3_prime_UTR_variant	Exon 12 of 12	1	NM_018327.4	ENSP00000381968.2

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71066 AN: 151820 Hom.: 16788 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.459

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.468 AC: 71149 AN: 151938 Hom.: 16816 Cov.: 32 AF XY: 0.474 AC XY: 35191 AN XY: 74274

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.460

Alfa AF: 0.460 Hom.: 1998

Bravo AF: 0.471

Asia WGS AF: 0.649 AC: 2256 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.60

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: rs2144134; hg19: chr20-13148152;