chr20-13167505-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

TASP1 Gene-Disease associations (from GenCC):

• Suleiman-El-Hattab syndrome

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.441 AC: 18265 AN: 41416

American (AMR) AF: 0.501 AC: 7652 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1548 AN: 3466

East Asian (EAS) AF: 0.629 AC: 3253 AN: 5172

South Asian (SAS) AF: 0.599 AC: 2886 AN: 4816

European-Finnish (FIN) AF: 0.452 AC: 4764 AN: 10548

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31190 AN: 67944

Other (OTH) AF: 0.460 AC: 970 AN: 2110

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
PhyloP100		-0.23

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: rs2144134; hg19: chr20-13148152;