rs143904989

Variant names:

• chr9-133671635-C-T
• rs143904989
• NM_001134707.2:c.2226G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-133671635-C-T
• chr9-133671635-C-A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001134707.2(SARDH):​c.2226G>A​(p.Ala742Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00022 in 1,598,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: SARDH NM_001134707.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.41
• Publications: 0 publications found

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]

SARDH Gene-Disease associations (from GenCC):

• sarcosinemia

  Inheritance: AR, Unknown Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 9-133671635-C-T is Benign according to our data. Variant chr9-133671635-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 729020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.41 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134707.2. 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
	SARDH	NM_001134707.2	MANE Select	c.2226G>A	p.Ala742Ala	synonymous	Exon 18 of 21	NP_001128179.1	Q9UL12-1
	SARDH	NM_007101.4		c.2226G>A	p.Ala742Ala	synonymous	Exon 18 of 21	NP_009032.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARDH	ENST00000439388.6	TSL:2 MANE Select	c.2226G>A	p.Ala742Ala	synonymous	Exon 18 of 21	ENSP00000403084.1	Q9UL12-1
	SARDH	ENST00000371872.8	TSL:1	c.2226G>A	p.Ala742Ala	synonymous	Exon 18 of 21	ENSP00000360938.4	Q9UL12-1
	SARDH	ENST00000859366.1		c.2406G>A	p.Ala802Ala	synonymous	Exon 19 of 22	ENSP00000529425.1

Frequencies

GnomAD3 genomes AF: 0.000434 AC: 66 AN: 152158 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

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: 0.000353

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000333 AC: 74 AN: 222348 AF XY: 0.000315

Gnomad AFR exome AF: 0.000149

Gnomad AMR exome AF: 0.00100

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000324

Gnomad OTH exome AF: 0.00125

GnomAD4 exome AF: 0.000197 AC: 285 AN: 1446328 Hom.: 0 Cov.: 66 AF XY: 0.000181 AC XY: 130 AN XY: 718144

African (AFR) AF: 0.000151 AC: 5 AN: 33202

American (AMR) AF: 0.000864 AC: 37 AN: 42824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25766

East Asian (EAS) AF: 0.00 AC: 0 AN: 39010

South Asian (SAS) AF: 0.0000239 AC: 2 AN: 83838

European-Finnish (FIN) AF: 0.0000196 AC: 1 AN: 50998

Middle Eastern (MID) AF: 0.00296 AC: 17 AN: 5740

European-Non Finnish (NFE) AF: 0.000179 AC: 198 AN: 1105134

Other (OTH) AF: 0.000418 AC: 25 AN: 59816

GnomAD4 genome AF: 0.000433 AC: 66 AN: 152276 Hom.: 0 Cov.: 33 AF XY: 0.000443 AC XY: 33 AN XY: 74460

African (AFR) AF: 0.000241 AC: 10 AN: 41554

American (AMR) AF: 0.00183 AC: 28 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68028

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.000343 Hom.: 0

Bravo AF: 0.000461

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.0
DANN	Benign	0.52
PhyloP100		-4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs143904989; hg19: chr9-136536757;