rs28608480

Variant names:

• chrM-12477-T-C
• rs28608480
• ENST00000361567.2:c.141T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP6_Moderate BP7 BS2

The ENST00000361567.2(MT-ND5):​c.141T>C​(p.Ser47Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0050 (AC: 307)
• Consequence: MT-ND5 ENST00000361567.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1 Possible-HCM-susceptibility
• Conservation: PhyloP100: 0.166
• Publications: 5 publications found

Genes affected

MT-ND5 (HGNC:7461): (mitochondrially encoded NADH dehydrogenase 5) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Leigh disease; and MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]

TRNL2 (HGNC:7491): (mitochondrially encoded tRNA leucine 2 (CUN))

TRNS2 (HGNC:7498): (mitochondrially encoded tRNA serine 2 (AGU/C))

TRNS2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP6: Variant M-12477-T-C is Benign according to our data. Variant chrM-12477-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3911706.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.166 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 303

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361567.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-ND5	ENST00000361567.2	TSL:6	c.141T>C	p.Ser47Ser	synonymous	Exon 1 of 1	ENSP00000354813.2
	MT-TS2	ENST00000387449.1	TSL:6	n.*212T>C		downstream_gene	N/A
	MT-TL2	ENST00000387456.1	TSL:6	n.*141T>C		downstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0050 AC: 307

Gnomad homoplasmic AF: 0.0054 AC: 303 AN: 56418

Gnomad heteroplasmic AF: 0.00012 AC: 7 AN: 56418

Alfa AF: 0.00510 Hom.: 117

Mitomap

Disease(s): Possible-HCM-susceptibility

Status: Reported

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism

Other links and lift over

dbSNP: rs28608480; hg19: chrM-12478;