chr12-113393140-T-A

Variant names:

• chr12-113393140-T-A
• NM_006843.3:c.788A>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006843.3(SDS):​c.788A>T​(p.Lys263Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SDS NM_006843.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.694

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.806

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDS	NM_006843.3	c.788A>T	p.Lys263Met	missense_variant	Exon 8 of 8	ENST00000257549.9	NP_006834.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDS	ENST00000257549.9	c.788A>T	p.Lys263Met	missense_variant	Exon 8 of 8	2	NM_006843.3	ENSP00000257549.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461424 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727004

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.92	D
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.76	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Pathogenic	1.2	D
MutationAssessor	Pathogenic	4.2	H
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.4	D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.66	P
Vest4		0.37
MutPred		0.57		Gain of catalytic residue at E267 (P = 0.0013);
MVP		0.94
MPC		0.89
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.84
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-113830945;