NM_006843.3:c.352G>C

Variant names:

• chr12-113398588-C-G
• rs751111047
• NM_006843.3:c.352G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006843.3(SDS):​c.352G>C​(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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SDS NM_006843.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0160
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13765463).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006843.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDS	NM_006843.3	MANE Select	c.352G>C	p.Glu118Gln	missense	Exon 5 of 8	NP_006834.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDS	ENST00000257549.9	TSL:2 MANE Select	c.352G>C	p.Glu118Gln	missense	Exon 5 of 8	ENSP00000257549.4	P20132
	SDS	ENST00000880860.1		c.394G>C	p.Glu132Gln	missense	Exon 5 of 8	ENSP00000550919.1
	SDS	ENST00000880862.1		c.364G>C	p.Glu122Gln	missense	Exon 5 of 8	ENSP00000550921.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152156 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.00000834 AC: 2 AN: 239788 AF XY: 0.00000770

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 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

African (AFR) AF: 0.00 AC: 0 AN: 32724

American (AMR) AF: 0.00 AC: 0 AN: 41260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25250

East Asian (EAS) AF: 0.00 AC: 0 AN: 39362

South Asian (SAS) AF: 0.00 AC: 0 AN: 84794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.00000727 AC: 8 AN: 1100724

Other (OTH) AF: 0.0000168 AC: 1 AN: 59386

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152156 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74316

African (AFR) AF: 0.0000241 AC: 1 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000776 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.14	T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.016
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.20
Sift	Benign	0.61	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
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs751111047; hg19: chr12-113836393;