20-13049098-T-G

Position:

• chr20-13049098-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018327.4(SPTLC3):​c.271T>G​(p.Cys91Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPTLC3 NM_018327.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.88

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.796

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTLC3	NM_018327.4	c.271T>G	p.Cys91Gly	missense_variant	2/12	ENST00000399002.7	NP_060797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTLC3	ENST00000399002.7	c.271T>G	p.Cys91Gly	missense_variant	2/12	1	NM_018327.4	ENSP00000381968	P1
SPTLC3	ENST00000476791.1	n.560T>G		non_coding_transcript_exon_variant	2/2	1
SPTLC3	ENST00000450297.1	c.190T>G	p.Cys64Gly	missense_variant	2/5	3		ENSP00000409125
SPTLC3	ENST00000434210.5	c.271T>G	p.Cys91Gly	missense_variant	3/4	3		ENSP00000389749

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.271T>G (p.C91G) alteration is located in exon 2 (coding exon 2) of the SPTLC3 gene. This alteration results from a T to G substitution at nucleotide position 271, causing the cysteine (C) at amino acid position 91 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.15	T;T;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Pathogenic	3.1	.;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-6.4	D;D;D
REVEL	Uncertain	0.57
Sift	Uncertain	0.014	D;T;T
Sift4G	Uncertain	0.025	D;T;D
Polyphen		0.24	.;B;.
Vest4		0.61
MutPred		0.63		Gain of disorder (P = 0.003);Gain of disorder (P = 0.003);.;
MVP		0.67
MPC		0.77
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.57
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-13029746;