rs41362547

Variant names:

• chrM-10044-A-G
• rs41362547
• unassigned_transcript_4807:c.54A>G

Variant summary

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

The ENST00000000000(TRNG):​c.54A>G​(p.Thr18Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0030 (AC: 185)
• Consequence: TRNG ENST00000000000 synonymous
• Scores: Mitotip Uncertain 11
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1 SIDS
• Conservation: PhyloP100: -0.125
• Publications: 3 publications found

Genes affected

TRNG (HGNC:7486): (mitochondrially encoded tRNA glycine)

MT-ND3 (HGNC:7458): (mitochondrially encoded NADH dehydrogenase 3) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Leigh disease; and Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

MT-CO3 (HGNC:7422): (mitochondrially encoded cytochrome c oxidase III) Predicted to enable electron transfer activity and oxidoreduction-driven active transmembrane transporter activity. Involved in respiratory chain complex IV assembly. Part of respiratory chain complex IV. Implicated in MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]

MT-CO3 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• hereditary recurrent myoglobinuria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cytochrome-c oxidase deficiency disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP6: Variant M-10044-A-G is Benign according to our data. Variant chrM-10044-A-G is described in ClinVar as Benign. ClinVar VariationId is 9613.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.125 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 397

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387429.1. 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-TG	ENST00000387429.1	TSL:6	n.54A>G		non_coding_transcript_exon	Exon 1 of 1
	MT-ND3	ENST00000361227.2	TSL:6	c.-15A>G		upstream_gene	N/A	ENSP00000355206.2	P03897
	MT-CO3	ENST00000362079.2	TSL:6	c.*54A>G		downstream_gene	N/A	ENSP00000354982.2	P00414

Frequencies

Mitomap GenBank AF: 0.0030 AC: 185

Gnomad homoplasmic AF: 0.0070 AC: 397 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Alfa AF: 0.00558 Hom.: 25

Mitomap

Disease(s): SIDS

Status: Unclear

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MELAS syndrome (1)
1	-	-	Sudden death (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	11
Hmtvar	Benign	0.30
PhyloP100		-0.13

Other links and lift over

dbSNP: rs41362547; hg19: chrM-10045;