9-133671511-G-A

Position:

• chr9-133671511-G-A

Variant summary

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

The NM_001134707.2(SARDH):​c.2326+24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 1,511,726 control chromosomes in the GnomAD database, including 187,519 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 0.54 (22593 hom., cov: 27)
  • Exomes 𝑓: 0.49 (164926 hom.)
• Consequence: SARDH NM_001134707.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SARDH	NM_001134707.2	c.2326+24C>T		intron_variant		ENST00000439388.6	NP_001128179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SARDH	ENST00000439388.6	c.2326+24C>T		intron_variant		2	NM_001134707.2	ENSP00000403084	P1
SARDH	ENST00000371872.8	c.2326+24C>T		intron_variant		1		ENSP00000360938	P1
SARDH	ENST00000371868.5	c.610+24C>T		intron_variant		2		ENSP00000360934

Frequencies

GnomAD3 genomes AF: 0.541 AC: 81441 AN: 150540 Hom.: 22572 Cov.: 27

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.524

GnomAD3 exomes AF: 0.529 AC: 106395 AN: 201028 Hom.: 29181 AF XY: 0.518 AC XY: 56641 AN XY: 109408

Gnomad AFR exome AF: 0.639

Gnomad AMR exome AF: 0.667

Gnomad ASJ exome AF: 0.486

Gnomad EAS exome AF: 0.789

Gnomad SAS exome AF: 0.509

Gnomad FIN exome AF: 0.466

Gnomad NFE exome AF: 0.451

Gnomad OTH exome AF: 0.514

GnomAD4 exome AF: 0.492 AC: 669348 AN: 1361072 Hom.: 164926 Cov.: 32 AF XY: 0.491 AC XY: 330006 AN XY: 672028

Gnomad4 AFR exome AF: 0.648

Gnomad4 AMR exome AF: 0.661

Gnomad4 ASJ exome AF: 0.492

Gnomad4 EAS exome AF: 0.815

Gnomad4 SAS exome AF: 0.511

Gnomad4 FIN exome AF: 0.464

Gnomad4 NFE exome AF: 0.468

Gnomad4 OTH exome AF: 0.504

GnomAD4 genome AF: 0.541 AC: 81510 AN: 150654 Hom.: 22593 Cov.: 27 AF XY: 0.543 AC XY: 39980 AN XY: 73594

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.783

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.521

Alfa AF: 0.485 Hom.: 22915

Bravo AF: 0.557

Asia WGS AF: 0.638 AC: 2221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.45
DANN	Benign	0.85

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: rs2797840; hg19: chr9-136536633; COSMIC: COSV64101142; COSMIC: COSV64101142;