12-113398588-C-G

Variant summary

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

The NM_006843.3(SDS):ā€‹c.352G>Cā€‹(p.Glu118Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000815 in 1,594,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000062 ( 0 hom. )

Consequence

SDS
NM_006843.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0160
Variant links:
Genes affected
SDS (HGNC:10691): (serine dehydratase) This gene encodes one of three enzymes that are involved in metabolizing serine and glycine. L-serine dehydratase converts L-serine to pyruvate and ammonia and requires pyridoxal phosphate as a cofactor. The encoded protein can also metabolize threonine to NH4+ and 2-ketobutyrate. The encoded protein is found predominantly in the liver. [provided by RefSeq, Jul 2008]

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=0.13765463).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SDSNM_006843.3 linkuse as main transcriptc.352G>C p.Glu118Gln missense_variant 5/8 ENST00000257549.9 NP_006834.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SDSENST00000257549.9 linkuse as main transcriptc.352G>C p.Glu118Gln missense_variant 5/82 NM_006843.3 ENSP00000257549 P1
SDSENST00000547342.1 linkuse as main transcriptc.634G>C p.Glu212Gln missense_variant 6/65 ENSP00000449061
SDSENST00000552280.5 linkuse as main transcriptc.153+968G>C intron_variant 3 ENSP00000449833
SDSENST00000553112.5 linkuse as main transcriptn.473G>C non_coding_transcript_exon_variant 5/62

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152156
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000834
AC:
2
AN:
239788
Hom.:
0
AF XY:
0.00000770
AC XY:
1
AN XY:
129852
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000182
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000624
AC:
9
AN:
1442286
Hom.:
0
Cov.:
32
AF XY:
0.00000419
AC XY:
3
AN XY:
715226
show subpopulations
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:
0.00000727
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152156
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74316
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:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000776
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1

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 GeneticsJun 21, 2022The c.352G>C (p.E118Q) alteration is located in exon 5 (coding exon 4) of the SDS gene. This alteration results from a G to C substitution at nucleotide position 352, causing the glutamic acid (E) at amino acid position 118 to be replaced by a glutamine (Q). 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
0.093
BayesDel_addAF
Benign
-0.0067
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
13
DANN
Benign
0.96
DEOGEN2
Uncertain
0.47
T;T
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.72
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.18
T;T
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.14
T;T
MetaSVM
Uncertain
-0.22
T
MutationAssessor
Benign
1.0
L;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
0.020
N;N
REVEL
Benign
0.20
Sift
Benign
0.61
T;T
Sift4G
Benign
0.60
T;.
Polyphen
0.0010
B;.
Vest4
0.22
MutPred
0.42
Loss of ubiquitination at K121 (P = 0.1045);.;
MVP
0.90
MPC
0.26
ClinPred
0.072
T
GERP RS
0.88
Varity_R
0.25
gMVP
0.37

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: rs751111047; hg19: chr12-113836393; API