12-113393092-C-T

Variant names:

• chr12-113393092-C-T
• rs766361189
• NM_006843.3:c.836G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006843.3(SDS):​c.836G>A​(p.Ser279Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S279T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SDS NM_006843.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3557892).

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.836G>A	p.Ser279Asn	missense	Exon 8 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.836G>A	p.Ser279Asn	missense	Exon 8 of 8	ENSP00000257549.4	P20132
	SDS	ENST00000880860.1		c.878G>A	p.Ser293Asn	missense	Exon 8 of 8	ENSP00000550919.1
	SDS	ENST00000880862.1		c.848G>A	p.Ser283Asn	missense	Exon 8 of 8	ENSP00000550921.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 250990 AF XY: 0.00000737

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461838 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D
Eigen	Benign	-0.036
Eigen_PC	Benign	0.037
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.36	T
MetaSVM	Pathogenic	0.92	D
MutationAssessor	Benign	1.8	L
PhyloP100		2.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.42
Sift	Benign	0.17	T
Sift4G	Benign	0.29	T
Polyphen		0.18	B
Vest4		0.10
MutPred		0.50		Gain of catalytic residue at A275 (P = 0.0012)
MVP		0.89
MPC		0.26
ClinPred		0.46	T
GERP RS		4.6
Varity_R		0.51
gMVP		0.34
Mutation Taster		=84/16	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: rs766361189; hg19: chr12-113830897;