chr9-133671511-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134707.2(SARDH):​c.2326+24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 1,511,726 control chromosomes in the GnomAD database, including 187,519 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 0.54 (22593 hom., cov: 27)
  • Exomes 𝑓: 0.49 (164926 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

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>T		intron	N/A	NP_001128179.1
	SARDH	NM_007101.4		c.2326+24C>T		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>T		intron	N/A	ENSP00000403084.1
	SARDH	ENST00000371872.8	TSL:1	c.2326+24C>T		intron	N/A	ENSP00000360938.4
	SARDH	ENST00000371868.5	TSL:2	c.610+24C>T		intron	N/A	ENSP00000360934.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 81441 AN: 150540 Hom.: 22572 Cov.: 27

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.524

GnomAD2 exomes AF: 0.529 AC: 106395 AN: 201028 AF XY: 0.518

Gnomad AFR exome AF: 0.639

Gnomad AMR exome AF: 0.667

Gnomad ASJ exome AF: 0.486

Gnomad EAS exome AF: 0.789

Gnomad FIN exome AF: 0.466

Gnomad NFE exome AF: 0.451

Gnomad OTH exome AF: 0.514

GnomAD4 exome AF: 0.492 AC: 669348 AN: 1361072 Hom.: 164926 Cov.: 32 AF XY: 0.491 AC XY: 330006 AN XY: 672028

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

African (AFR) AF: 0.648 AC: 20270 AN: 31302

American (AMR) AF: 0.661 AC: 25018 AN: 37842

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 11505 AN: 23400

East Asian (EAS) AF: 0.815 AC: 29871 AN: 36660

South Asian (SAS) AF: 0.511 AC: 40697 AN: 79702

European-Finnish (FIN) AF: 0.464 AC: 22509 AN: 48562

Middle Eastern (MID) AF: 0.569 AC: 2853 AN: 5010

European-Non Finnish (NFE) AF: 0.468 AC: 488408 AN: 1042584

Other (OTH) AF: 0.504 AC: 28217 AN: 56010

⚠️ 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: 0.541 AC: 81510 AN: 150654 Hom.: 22593 Cov.: 27 AF XY: 0.543 AC XY: 39980 AN XY: 73594

African (AFR) AF: 0.642 AC: 26295 AN: 40952

American (AMR) AF: 0.582 AC: 8837 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1727 AN: 3454

East Asian (EAS) AF: 0.783 AC: 3953 AN: 5048

South Asian (SAS) AF: 0.524 AC: 2479 AN: 4734

European-Finnish (FIN) AF: 0.464 AC: 4831 AN: 10410

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31695 AN: 67584

Other (OTH) AF: 0.521 AC: 1087 AN: 2086

Alfa AF: 0.492 Hom.: 63049

Bravo AF: 0.557

Asia WGS AF: 0.638 AC: 2221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.45
DANN	Benign	0.85
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV64101142; COSMIC: COSV64101142;