SPTLC2 p.Gln300His

Variant names:

• chr14-77557097-C-A
• NM_004863.4:c.900G>T
• SPTLC2 p.Gln300His

Your query was ambiguous. Multiple possible variants found:

• chr14-77557097-C-A
• chr14-77557097-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004863.4(SPTLC2):​c.900G>T​(p.Gln300His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q300Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPTLC2 NM_004863.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 0 publications found

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]

SPTLC2 Gene-Disease associations (from GenCC):

• neuropathy, hereditary sensory and autonomic, type 1C

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: STRONG Submitted by: ClinGen
• hereditary sensory and autonomic neuropathy type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.749

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004863.4. 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
	SPTLC2	NM_004863.4	MANE Select	c.900G>T	p.Gln300His	missense	Exon 7 of 12	NP_004854.1	O15270

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTLC2	ENST00000216484.7	TSL:1 MANE Select	c.900G>T	p.Gln300His	missense	Exon 7 of 12	ENSP00000216484.2	O15270
	SPTLC2	ENST00000554901.1	TSL:1	c.708G>T	p.Gln236His	missense	Exon 6 of 9	ENSP00000452189.1	H0YJV2
	SPTLC2	ENST00000950640.1		c.996G>T	p.Gln332His	missense	Exon 8 of 13	ENSP00000620699.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.87	D
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Pathogenic	0.46	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	0.76	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.0
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Pathogenic	0.80
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0020	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.91
Mutation Taster		=32/68	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-78023440;