rs1164824967

chr14-77616536-C-Gchr14-77616536-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004863.4(SPTLC2):c.44G>C(p.Arg15Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,383,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R15Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: SPTLC2 NM_004863.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87

Genes affected

SPTLC2 (HGNC:11278): (serine palmitoyltransferase long chain base subunit 2) This gene encodes a long chain base subunit of serine palmitoyltransferase. Serine palmitoyltransferase, which consists of two different subunits, is the key enzyme in sphingolipid biosynthesis. It catalyzes the pyridoxal-5-prime-phosphate-dependent condensation of L-serine and palmitoyl-CoA to 3-oxosphinganine. Mutations in this gene were identified in patients with hereditary sensory neuropathy type I. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37267298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPTLC2	NM_004863.4	c.44G>C	p.Arg15Pro	missense_variant	1/12	ENST00000216484.7
SPTLC2	XM_011537384.3	c.44G>C	p.Arg15Pro	missense_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTLC2	ENST00000216484.7	c.44G>C	p.Arg15Pro	missense_variant	1/12	1	NM_004863.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000289 AC: 4 AN: 1383366 Hom.: 0 Cov.: 31 AF XY: 0.00000439 AC XY: 3 AN XY: 682946

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000371

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.70	T
M_CAP	Pathogenic	0.93	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	0.99	N
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.92	N
REVEL	Uncertain	0.55
Sift	Benign	0.040	D
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.40
MutPred		0.36		Loss of MoRF binding (P = 2e-04);
MVP		0.96
MPC		1.1
ClinPred		0.25	T
GERP RS		3.1
Varity_R		0.32
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1164824967; hg19: chr14-78082879;