12-113398799-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_006843.3(SDS):​c.241G>A​(p.Val81Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,612,552 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (4 hom.)
• Consequence: SDS NM_006843.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.306
• Publications: 3 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021097481).
• BP6: Variant 12-113398799-C-T is Benign according to our data. Variant chr12-113398799-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 708699.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

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>A	p.Val81Ile	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>A	p.Val81Ile	missense	Exon 4 of 8	ENSP00000257549.4	P20132
	SDS	ENST00000880860.1		c.283G>A	p.Val95Ile	missense	Exon 4 of 8	ENSP00000550919.1
	SDS	ENST00000880862.1		c.253G>A	p.Val85Ile	missense	Exon 4 of 8	ENSP00000550921.1

Frequencies

GnomAD3 genomes AF: 0.00138 AC: 210 AN: 152236 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000470

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00223

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00145 AC: 355 AN: 245454 AF XY: 0.00144

Gnomad AFR exome AF: 0.000701

Gnomad AMR exome AF: 0.000907

Gnomad ASJ exome AF: 0.000905

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000518

Gnomad NFE exome AF: 0.00243

Gnomad OTH exome AF: 0.00233

GnomAD4 exome AF: 0.00191 AC: 2787 AN: 1460198 Hom.: 4 Cov.: 32 AF XY: 0.00183 AC XY: 1328 AN XY: 726382

African (AFR) AF: 0.000748 AC: 25 AN: 33430

American (AMR) AF: 0.00108 AC: 48 AN: 44532

Ashkenazi Jewish (ASJ) AF: 0.00111 AC: 29 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.000464 AC: 40 AN: 86122

European-Finnish (FIN) AF: 0.000718 AC: 38 AN: 52896

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5762

European-Non Finnish (NFE) AF: 0.00226 AC: 2510 AN: 1111434

Other (OTH) AF: 0.00154 AC: 93 AN: 60282

GnomAD4 genome AF: 0.00137 AC: 209 AN: 152354 Hom.: 0 Cov.: 32 AF XY: 0.00129 AC XY: 96 AN XY: 74502

African (AFR) AF: 0.000721 AC: 30 AN: 41586

American (AMR) AF: 0.000980 AC: 15 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.000470 AC: 5 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00223 AC: 152 AN: 68026

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00175 Hom.: 0

Bravo AF: 0.00127

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00186 AC: 16

ExAC AF: 0.00135 AC: 164

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	0.036
DANN	Benign	0.78
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.021	T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	-0.37	N
PhyloP100		-0.31
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.13	N
REVEL	Uncertain	0.34
Sift	Benign	1.0	T
Sift4G	Benign	0.81	T
Polyphen		0.0	B
Vest4		0.11
MVP		0.49
MPC		0.21
ClinPred		0.0051	T
GERP RS		-7.6
Varity_R		0.047
gMVP		0.20
Mutation Taster		=98/2	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;