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GeneBe

12-113397331-T-C

Variant summary

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

The NM_006843.3(SDS):c.487A>G(p.Ile163Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SDS
NM_006843.3 missense

Scores

3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.698
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=0.2039707).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SDSNM_006843.3 linkuse as main transcriptc.487A>G p.Ile163Val missense_variant 6/8 ENST00000257549.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SDSENST00000257549.9 linkuse as main transcriptc.487A>G p.Ile163Val missense_variant 6/82 NM_006843.3 P1
SDSENST00000552280.5 linkuse as main transcriptc.215A>G p.His72Arg missense_variant 3/33
SDSENST00000553112.5 linkuse as main transcriptn.608A>G non_coding_transcript_exon_variant 6/62

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250520
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135462
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461650
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727096
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113
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 GeneticsDec 02, 2022The c.487A>G (p.I163V) alteration is located in exon 6 (coding exon 5) of the SDS gene. This alteration results from a A to G substitution at nucleotide position 487, causing the isoleucine (I) at amino acid position 163 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
0.084
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.13
Cadd
Benign
11
Dann
Benign
0.97
DEOGEN2
Benign
0.17
T
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.30
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.23
T
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.20
T
MetaSVM
Uncertain
0.018
D
MutationTaster
Benign
1.0
D
PROVEAN
Benign
0.42
N
REVEL
Benign
0.063
Sift
Benign
0.35
T
Sift4G
Benign
0.36
T
MutPred
0.46
Gain of catalytic residue at K68 (P = 0.0011);
MVP
0.29
ClinPred
0.083
T
GERP RS
4.5

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: rs759287194; hg19: chr12-113835136; API