12-113398519-T-G

Position:

• chr12-113398519-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006843.3(SDS):​c.421A>C​(p.Ile141Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SDS NM_006843.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.42

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDS	NM_006843.3	c.421A>C	p.Ile141Leu	missense_variant	5/8	ENST00000257549.9	NP_006834.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDS	ENST00000257549.9	c.421A>C	p.Ile141Leu	missense_variant	5/8	2	NM_006843.3	ENSP00000257549	P1
SDS	ENST00000547342.1	c.703A>C	p.Ile235Leu	missense_variant	6/6	5		ENSP00000449061
SDS	ENST00000552280.5	c.153+1037A>C		intron_variant		3		ENSP00000449833
SDS	ENST00000553112.5	n.542A>C		non_coding_transcript_exon_variant	5/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2023

The c.421A>C (p.I141L) alteration is located in exon 5 (coding exon 4) of the SDS gene. This alteration results from a A to C substitution at nucleotide position 421, causing the isoleucine (I) at amino acid position 141 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D;T
Eigen	Benign	-0.027
Eigen_PC	Benign	0.092
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;T
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Uncertain	0.73	D
MutationAssessor	Benign	1.3	L;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.79	N;N
REVEL	Uncertain	0.63
Sift	Benign	0.44	T;T
Sift4G	Benign	0.79	T;.
Polyphen		0.017	B;.
Vest4		0.54
MutPred		0.58		Gain of catalytic residue at L140 (P = 0);.;
MVP		0.76
MPC		0.32
ClinPred		0.77	D
GERP RS		4.3
Varity_R		0.54
gMVP		0.78

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-113836324;