9-133696245-G-C

Variant names:

• chr9-133696245-G-C
• rs2502740
• NM_001134707.2:c.1785C>G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001134707.2(SARDH):​c.1785C>G​(p.Ser595Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 1,613,854 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (34 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (40 hom.)
• Consequence: SARDH NM_001134707.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.51

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 9-133696245-G-C is Benign according to our data. Variant chr9-133696245-G-C is described in ClinVar as [Benign]. Clinvar id is 785297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.51 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1630/152086) while in subpopulation AFR AF= 0.0375 (1556/41474). AF 95% confidence interval is 0.036. There are 34 homozygotes in gnomad4. There are 733 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SARDH	NM_001134707.2	c.1785C>G	p.Ser595Ser	synonymous_variant	Exon 14 of 21	ENST00000439388.6	NP_001128179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SARDH	ENST00000439388.6	c.1785C>G	p.Ser595Ser	synonymous_variant	Exon 14 of 21	2	NM_001134707.2	ENSP00000403084.1
SARDH	ENST00000371872.8	c.1785C>G	p.Ser595Ser	synonymous_variant	Exon 14 of 21	1		ENSP00000360938.4
SARDH	ENST00000427237.6	c.1785C>G	p.Ser595Ser	synonymous_variant	Exon 14 of 15	2		ENSP00000394210.2
SARDH	ENST00000371868.5	c.69C>G	p.Ser23Ser	synonymous_variant	Exon 2 of 9	2		ENSP00000360934.1

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1629 AN: 151968 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0376

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00353

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00672

GnomAD3 exomes AF: 0.00300 AC: 754 AN: 251106 Hom.: 19 AF XY: 0.00203 AC XY: 276 AN XY: 135756

Gnomad AFR exome AF: 0.0401

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000793

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.00114 AC: 1669 AN: 1461768 Hom.: 40 Cov.: 51 AF XY: 0.000938 AC XY: 682 AN XY: 727196

Gnomad4 AFR exome AF: 0.0417

Gnomad4 AMR exome AF: 0.00288

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.00202

GnomAD4 genome AF: 0.0107 AC: 1630 AN: 152086 Hom.: 34 Cov.: 32 AF XY: 0.00986 AC XY: 733 AN XY: 74334

Gnomad4 AFR AF: 0.0375

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.00665

Alfa AF: 0.0000318 Hom.: 11631

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.010
DANN	Benign	0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2502740; hg19: chr9-136561367;