chr9-133670733-C-T

Variant names:

• chr9-133670733-C-T
• rs147854817
• NM_001134707.2:c.2346G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001134707.2(SARDH):​c.2346G>A​(p.Ala782Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00733 in 1,588,182 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0054 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0075 (62 hom.)
• Consequence: SARDH NM_001134707.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -5.98
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-133670733-C-T is Benign according to our data. Variant chr9-133670733-C-T is described in ClinVar as Benign. ClinVar VariationId is 791575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.98 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 Unknown,AR gene

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.2346G>A	p.Ala782Ala	synonymous	Exon 19 of 21	NP_001128179.1	Q9UL12-1
	SARDH	NM_007101.4		c.2346G>A	p.Ala782Ala	synonymous	Exon 19 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.2346G>A	p.Ala782Ala	synonymous	Exon 19 of 21	ENSP00000403084.1	Q9UL12-1
	SARDH	ENST00000371872.8	TSL:1	c.2346G>A	p.Ala782Ala	synonymous	Exon 19 of 21	ENSP00000360938.4	Q9UL12-1
	SARDH	ENST00000859366.1		c.2526G>A	p.Ala842Ala	synonymous	Exon 20 of 22	ENSP00000529425.1

Frequencies

GnomAD3 genomes AF: 0.00541 AC: 824 AN: 152190 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00216

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00584 AC: 1265 AN: 216476 AF XY: 0.00583

Gnomad AFR exome AF: 0.00204

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.00395

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00249

Gnomad NFE exome AF: 0.0111

Gnomad OTH exome AF: 0.00446

GnomAD4 exome AF: 0.00753 AC: 10815 AN: 1435874 Hom.: 62 Cov.: 32 AF XY: 0.00736 AC XY: 5244 AN XY: 712418

African (AFR) AF: 0.00129 AC: 42 AN: 32528

American (AMR) AF: 0.00174 AC: 72 AN: 41276

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 84 AN: 24310

East Asian (EAS) AF: 0.00 AC: 0 AN: 39330

South Asian (SAS) AF: 0.000729 AC: 60 AN: 82256

European-Finnish (FIN) AF: 0.00357 AC: 182 AN: 50998

Middle Eastern (MID) AF: 0.00695 AC: 39 AN: 5612

European-Non Finnish (NFE) AF: 0.00909 AC: 9999 AN: 1100436

Other (OTH) AF: 0.00570 AC: 337 AN: 59128

GnomAD4 genome AF: 0.00541 AC: 824 AN: 152308 Hom.: 5 Cov.: 33 AF XY: 0.00486 AC XY: 362 AN XY: 74476

African (AFR) AF: 0.00156 AC: 65 AN: 41568

American (AMR) AF: 0.00137 AC: 21 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00216 AC: 23 AN: 10630

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

European-Non Finnish (NFE) AF: 0.0101 AC: 686 AN: 68016

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00769 Hom.: 1

Bravo AF: 0.00528

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.80
CADD	Benign	0.14
DANN	Benign	0.78
PhyloP100		-6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs147854817; hg19: chr9-136535855;