MDH2 p.Ser3Ser

Variant names:

• chr7-76048166-C-C
• ENST00000315758.10:c.

Your query was ambiguous. Multiple possible variants found:

• chr7-76048167--
• chr7-76048169-C-T
• chr7-76048169-C-A
• chr7-76048169-C-G
• chr7-76048167-TC-AG
• chr7-76048167-TCC-AGT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000315758.10(MDH2):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 35)
• Consequence: MDH2 ENST00000315758.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 0 publications found

Genes affected

MDH2 (HGNC:6971): (malate dehydrogenase 2) Malate dehydrogenase catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle. The protein encoded by this gene is localized to the mitochondria and may play pivotal roles in the malate-aspartate shuttle that operates in the metabolic coordination between cytosol and mitochondria. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

STYXL1 (HGNC:18165): (serine/threonine/tyrosine interacting like 1) Enables protein phosphatase binding activity; protein phosphatase inhibitor activity; and pseudophosphatase activity. Involved in several processes, including negative regulation of phosphoprotein phosphatase activity; negative regulation of stress granule assembly; and positive regulation of intrinsic apoptotic signaling pathway. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000315758.10. 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
	STYXL1	NM_001317785.2	MANE Select	c.		upstream_gene	N/A	NP_001304714.1	Q9Y6J8-1
	STYXL1	NM_001317786.2		c.		upstream_gene	N/A	NP_001304715.1	Q9Y6J8-1
	STYXL1	NM_016086.3		c.		upstream_gene	N/A	NP_057170.1	Q9Y6J8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDH2	ENST00000315758.10	TSL:1 MANE Select	c.		intron	N/A	ENSP00000327070.5	P40926-1
	MDH2	ENST00000971443.1		c.		intron	N/A	ENSP00000641502.1
	MDH2	ENST00000854579.1		c.		intron	N/A	ENSP00000524638.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-75677484;