rs2502741

chr9-133697918-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134707.2(SARDH):c.1669-1557T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 150,604 control chromosomes in the GnomAD database, including 16,388 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (16388 hom., cov: 28)
• Consequence: SARDH NM_001134707.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316

Genes affected

SARDH (HGNC:10536): (sarcosine dehydrogenase) This gene encodes an enzyme localized to the mitochondrial matrix which catalyzes the oxidative demethylation of sarcosine. This enzyme is distinct from another mitochondrial matrix enzyme, dimethylglycine dehydrogenase, which catalyzes a reaction resulting in the formation of sarcosine. Mutations in this gene are associated with sarcosinemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SARDH	NM_001134707.2	c.1669-1557T>C		intron_variant		ENST00000439388.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SARDH	ENST00000439388.6	c.1669-1557T>C		intron_variant		2	NM_001134707.2	P1
SARDH	ENST00000371872.8	c.1669-1557T>C		intron_variant		1		P1
SARDH	ENST00000371868.5	c.-48-1557T>C		intron_variant		2
SARDH	ENST00000427237.6	c.1669-1557T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.465 AC: 69976 AN: 150494 Hom.: 16385 Cov.: 28

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.497

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.465 AC: 70008 AN: 150604 Hom.: 16388 Cov.: 28 AF XY: 0.465 AC XY: 34210 AN XY: 73498

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.500

Alfa AF: 0.477 Hom.: 1910

Bravo AF: 0.465

Asia WGS AF: 0.490 AC: 1704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.3
Dann	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs2502741; hg19: chr9-136563040;