12-113398519-T-C

Variant names:

• chr12-113398519-T-C
• rs778349566
• NM_006843.3:c.421A>G

Variant summary

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

The NM_006843.3(SDS):​c.421A>G​(p.Ile141Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,436,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. I141F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SDS NM_006843.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.42
• 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=0.32435477).

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.421A>G	p.Ile141Val	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.421A>G	p.Ile141Val	missense	Exon 5 of 8	ENSP00000257549.4	P20132
	SDS	ENST00000880860.1		c.463A>G	p.Ile155Val	missense	Exon 5 of 8	ENSP00000550919.1
	SDS	ENST00000880862.1		c.433A>G	p.Ile145Val	missense	Exon 5 of 8	ENSP00000550921.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000426 AC: 1 AN: 234944 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000577

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1436658 Hom.: 0 Cov.: 30 AF XY: 0.00000280 AC XY: 2 AN XY: 713486

African (AFR) AF: 0.00 AC: 0 AN: 32052

American (AMR) AF: 0.00 AC: 0 AN: 37974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25158

East Asian (EAS) AF: 0.0000761 AC: 3 AN: 39420

South Asian (SAS) AF: 0.00 AC: 0 AN: 83604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100300

Other (OTH) AF: 0.00 AC: 0 AN: 59262

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.045	D
MutationAssessor	Benign	1.1	L
PhyloP100		3.4
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.68	N
REVEL	Uncertain	0.36
Sift	Benign	0.17	T
Sift4G	Benign	0.28	T
Polyphen		0.087	B
Vest4		0.22
MutPred		0.57		Gain of catalytic residue at L140 (P = 0)
MVP		0.69
MPC		0.26
ClinPred		0.40	T
GERP RS		4.3
Varity_R		0.23
gMVP		0.52
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs778349566; hg19: chr12-113836324;