chr9-133671511-G-C

Variant names:

• chr9-133671511-G-C
• rs2797840
• NM_001134707.2:c.2326+24C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. 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
• Publications: 10 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: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARDH	NM_001134707.2	MANE Select	c.2326+24C>G		intron	N/A	NP_001128179.1
	SARDH	NM_007101.4		c.2326+24C>G		intron	N/A	NP_009032.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARDH	ENST00000439388.6	TSL:2 MANE Select	c.2326+24C>G		intron	N/A	ENSP00000403084.1
	SARDH	ENST00000371872.8	TSL:1	c.2326+24C>G		intron	N/A	ENSP00000360938.4
	SARDH	ENST00000371868.5	TSL:2	c.610+24C>G		intron	N/A	ENSP00000360934.1

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

GnomAD2 exomes AF: 0.000114 AC: 23 AN: 201028 AF XY: 0.000110

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00153 AC: 48 AN: 31448

American (AMR) AF: 0.00160 AC: 61 AN: 38016

Ashkenazi Jewish (ASJ) AF: 0.00119 AC: 28 AN: 23534

East Asian (EAS) AF: 0.00286 AC: 105 AN: 36744

South Asian (SAS) AF: 0.000287 AC: 23 AN: 80010

European-Finnish (FIN) AF: 0.00156 AC: 76 AN: 48770

Middle Eastern (MID) AF: 0.000791 AC: 4 AN: 5060

European-Non Finnish (NFE) AF: 0.000791 AC: 831 AN: 1050280

Other (OTH) AF: 0.00105 AC: 59 AN: 56382

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000976 AC: 4 AN: 41002

American (AMR) AF: 0.0000658 AC: 1 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5056

South Asian (SAS) AF: 0.00 AC: 0 AN: 4744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10428

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67662

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 63049

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.27
DANN	Benign	0.35
PhyloP100		-0.26
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: rs2797840; hg19: chr9-136536633;