NM_006843.3:c.241G>T

Variant names:

• chr12-113398799-C-A
• rs141811663
• NM_006843.3:c.241G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006843.3(SDS):​c.241G>T​(p.Val81Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. V81I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SDS NM_006843.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.782

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.241G>T	p.Val81Phe	missense	Exon 4 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.241G>T	p.Val81Phe	missense	Exon 4 of 8	ENSP00000257549.4	P20132
	SDS	ENST00000880860.1		c.283G>T	p.Val95Phe	missense	Exon 4 of 8	ENSP00000550919.1
	SDS	ENST00000880862.1		c.253G>T	p.Val85Phe	missense	Exon 4 of 8	ENSP00000550921.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	5.0
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.81	D
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.53	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	0.77	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		-0.31
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.016	D
Polyphen		0.57	P
Vest4		0.48
MutPred		0.61		Gain of catalytic residue at Q78 (P = 8e-04)
MVP		0.66
MPC		0.82
ClinPred		0.96	D
GERP RS		-7.6
Varity_R		0.29
gMVP		0.83
Mutation Taster		=64/36	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: rs141811663; hg19: chr12-113836604;