rs129925

Positions:

• chr9-133664644-C-G
• chr9-133664644-C-T

Variant summary

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

The NM_001134707.2(SARDH):​c.2632-630G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 152,300 control chromosomes in the GnomAD database, including 111 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 0.030 (111 hom., cov: 33)
• Consequence: SARDH NM_001134707.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.988

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SARDH	NM_001134707.2	c.2632-630G>C		intron_variant		ENST00000439388.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SARDH	ENST00000439388.6	c.2632-630G>C		intron_variant		2	NM_001134707.2	P1
SARDH	ENST00000371872.8	c.2632-630G>C		intron_variant		1		P1
SARDH	ENST00000371868.5	c.982-630G>C		intron_variant		2
SARDH	ENST00000469828.1	n.390-630G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0297 AC: 4513 AN: 152182 Hom.: 112 Cov.: 33

Gnomad AFR AF: 0.0398

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0252

Gnomad ASJ AF: 0.0789

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0199

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0194

Gnomad OTH AF: 0.0287

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

GnomAD4 genome AF: 0.0296 AC: 4508 AN: 152300 Hom.: 111 Cov.: 33 AF XY: 0.0313 AC XY: 2333 AN XY: 74466

Gnomad4 AFR AF: 0.0397

Gnomad4 AMR AF: 0.0251

Gnomad4 ASJ AF: 0.0789

Gnomad4 EAS AF: 0.00598

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0199

Gnomad4 NFE AF: 0.0194

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0111 Hom.: 3

Bravo AF: 0.0274

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.34
DANN	Benign	0.47

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

LitVar

Other links and lift over

dbSNP: rs129925; hg19: chr9-136529766;