NM_001134707.2:c.916-2203T>C

Variant names:

• chr9-133721245-A-G
• rs7040170
• NM_001134707.2:c.916-2203T>C

Variant summary

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

The NM_001134707.2(SARDH):​c.916-2203T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,226 control chromosomes in the GnomAD database, including 3,545 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 0.21 (3545 hom., cov: 33)
• Consequence: SARDH NM_001134707.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SARDH	NM_001134707.2	c.916-2203T>C		intron_variant	Intron 6 of 20	ENST00000439388.6	NP_001128179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SARDH	ENST00000439388.6	c.916-2203T>C		intron_variant	Intron 6 of 20	2	NM_001134707.2	ENSP00000403084.1
SARDH	ENST00000371872.8	c.916-2203T>C		intron_variant	Intron 6 of 20	1		ENSP00000360938.4
SARDH	ENST00000371867.5	c.649-2203T>C		intron_variant	Intron 5 of 6	1		ENSP00000360933.1
SARDH	ENST00000427237.6	c.916-2203T>C		intron_variant	Intron 6 of 14	2		ENSP00000394210.2

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31912 AN: 152108 Hom.: 3541 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.0820

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.242

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.210 AC: 31944 AN: 152226 Hom.: 3545 Cov.: 33 AF XY: 0.208 AC XY: 15468 AN XY: 74412

African (AFR) AF: 0.187 AC: 7750 AN: 41534

American (AMR) AF: 0.220 AC: 3363 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 976 AN: 3470

East Asian (EAS) AF: 0.0826 AC: 428 AN: 5180

South Asian (SAS) AF: 0.188 AC: 908 AN: 4826

European-Finnish (FIN) AF: 0.190 AC: 2015 AN: 10600

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15485 AN: 68006

Other (OTH) AF: 0.247 AC: 521 AN: 2112

Alfa AF: 0.223 Hom.: 15538

Bravo AF: 0.210

Asia WGS AF: 0.176 AC: 611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.6
DANN	Benign	0.47
PhyloP100		-0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7040170; hg19: chr9-136586367;