9-133671511-G-C

Position:

• chr9-133671511-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001134707.2(SARDH):​c.2326+24C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000815 in 1,521,090 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00090 (0 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0000332 AC: 5 AN: 150732 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000978

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000659

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000114 AC: 23 AN: 201028 Hom.: 0 AF XY: 0.000110 AC XY: 12 AN XY: 109408

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000256

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000392

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000558

Gnomad NFE exome AF: 0.0000556

Gnomad OTH exome AF: 0.000810

GnomAD4 exome AF: 0.000901 AC: 1235 AN: 1370244 Hom.: 0 Cov.: 32 AF XY: 0.000894 AC XY: 605 AN XY: 676364

Gnomad4 AFR exome AF: 0.00153

Gnomad4 AMR exome AF: 0.00160

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.00286

Gnomad4 SAS exome AF: 0.000287

Gnomad4 FIN exome AF: 0.00156

Gnomad4 NFE exome AF: 0.000791

Gnomad4 OTH exome AF: 0.00105

GnomAD4 genome AF: 0.0000331 AC: 5 AN: 150846 Hom.: 0 Cov.: 27 AF XY: 0.0000271 AC XY: 2 AN XY: 73694

Gnomad4 AFR AF: 0.0000976

Gnomad4 AMR AF: 0.0000658

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.27
DANN	Benign	0.35

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;