14-34462194-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138288.4(SPTSSA):​c.14C>T​(p.Ala5Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SPTSSA
NM_138288.4 missense

Scores

2
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.21
Variant links:
Genes affected
SPTSSA (HGNC:20361): (serine palmitoyltransferase small subunit A) Serine palmitoyltransferase (SPT; EC 2.3.1.50) catalyzes the first committed and rate-limiting step in sphingolipid biosynthesis. SSSPTA is a small SPT subunit that stimulates SPT activity and confers acyl-CoA preference to the SPT catalytic heterodimer of SPTLC1 (MIM 605712) and either SPTLC2 (MIM 605713) or SPTLC3 (MIM 611120) (Han et al., 2009 [PubMed 19416851]).[supplied by OMIM, Nov 2010]
EGLN3 (HGNC:14661): (egl-9 family hypoxia inducible factor 3) Enables peptidyl-proline 4-dioxygenase activity. Involved in several processes, including activation of cysteine-type endopeptidase activity involved in apoptotic process; peptidyl-proline hydroxylation to 4-hydroxy-L-proline; and response to hypoxia. Located in cytosol and nucleus. Implicated in renal cell carcinoma. Biomarker of clear cell renal cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16360408).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SPTSSANM_138288.4 linkuse as main transcriptc.14C>T p.Ala5Val missense_variant 1/2 ENST00000298130.5 NP_612145.2 Q969W0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SPTSSAENST00000298130.5 linkuse as main transcriptc.14C>T p.Ala5Val missense_variant 1/21 NM_138288.4 ENSP00000298130.4 Q969W0
EGLN3ENST00000551935.5 linkuse as main transcriptn.59+522C>T intron_variant 4

Frequencies

GnomAD3 genomes
Cov.:
29
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1378214
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
685800
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
29
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 01, 2024The c.14C>T (p.A5V) alteration is located in exon 1 (coding exon 1) of the SPTSSA gene. This alteration results from a C to T substitution at nucleotide position 14, causing the alanine (A) at amino acid position 5 to be replaced by a valine (V). 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
0.12
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.019
T
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.39
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.49
T
M_CAP
Pathogenic
0.50
D
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-1.0
T
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-0.33
N
REVEL
Benign
0.13
Sift
Benign
0.27
T
Sift4G
Benign
0.32
T
Polyphen
0.22
B
Vest4
0.13
MutPred
0.41
Gain of catalytic residue at M4 (P = 5e-04);
MVP
0.043
MPC
0.28
ClinPred
0.95
D
GERP RS
2.2
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6
Varity_R
0.12
gMVP
0.86

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1878635964; hg19: chr14-34931400; COSMIC: COSV99987759; API