1-246759053-C-T

Variant summary

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

The NM_016002.3(SCCPDH):​c.715C>T​(p.Arg239Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,604,664 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

SCCPDH
NM_016002.3 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28
Variant links:
Genes affected
SCCPDH (HGNC:24275): (saccharopine dehydrogenase (putative)) Predicted to enable oxidoreductase activity. Predicted to be involved in glycolipid biosynthetic process. Located in lipid droplet and midbody. [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=0.24883404).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SCCPDHNM_016002.3 linkc.715C>T p.Arg239Trp missense_variant Exon 7 of 12 ENST00000366510.4 NP_057086.2 Q8NBX0A0A384NPM7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SCCPDHENST00000366510.4 linkc.715C>T p.Arg239Trp missense_variant Exon 7 of 12 1 NM_016002.3 ENSP00000355467.3 Q8NBX0

Frequencies

GnomAD3 genomes
AF:
0.000138
AC:
21
AN:
152104
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000189
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000191
AC:
48
AN:
251326
Hom.:
0
AF XY:
0.000133
AC XY:
18
AN XY:
135824
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.000323
Gnomad NFE exome
AF:
0.000290
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000186
AC:
270
AN:
1452560
Hom.:
1
Cov.:
27
AF XY:
0.000169
AC XY:
122
AN XY:
723348
show subpopulations
Gnomad4 AFR exome
AF:
0.0000301
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000356
Gnomad4 NFE exome
AF:
0.000211
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000138
AC:
21
AN:
152104
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000189
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000195
Hom.:
0
Bravo
AF:
0.000140
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000272
AC:
33
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.715C>T (p.R239W) alteration is located in exon 7 (coding exon 7) of the SCCPDH gene. This alteration results from a C to T substitution at nucleotide position 715, causing the arginine (R) at amino acid position 239 to be replaced by a tryptophan (W). 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
0.19
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T
Eigen
Benign
0.11
Eigen_PC
Benign
0.088
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.70
T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.25
T
MetaSVM
Benign
-0.62
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-3.3
D
REVEL
Benign
0.27
Sift
Uncertain
0.024
D
Sift4G
Uncertain
0.014
D
Polyphen
1.0
D
Vest4
0.19
MVP
0.67
MPC
0.55
ClinPred
0.24
T
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.093
gMVP
0.67

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

LitVar

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

Other links and lift over

dbSNP: rs201518244; hg19: chr1-246922355; API