ENST00000361567.2:c.474A>G

Variant names:

• chrM-12810-A-G
• rs28359174
• ENST00000361567.2:c.474A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP6_Moderate BP7 BA1

The ENST00000361567.2(MT-ND5):​c.474A>G​(p.Trp158Trp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.017 (AC: 1037)
• Consequence: MT-ND5 ENST00000361567.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.373
• Publications: 9 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]

MT-ND5 Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: STRONG, SUPPORTIVE Submitted by: G2P, Orphanet
• maternally-inherited Leigh syndrome

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

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

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP6: Variant M-12810-A-G is Benign according to our data. Variant chrM-12810-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 235499.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.373 with no splicing effect.
• BA1: High frequency in mitomap database: 0.017

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.474A>G	p.Trp158Trp	synonymous	Exon 1 of 1	ENSP00000354813.2	P03915

Frequencies

Mitomap GenBank AF: 0.017 AC: 1037

Gnomad homoplasmic AF: 0.030 AC: 1715 AN: 56410

Gnomad heteroplasmic AF: 0.00018 AC: 10 AN: 56410

Alfa AF: 0.00768 Hom.: 34

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.45	T
PhyloP100		-0.37
GERP RS		-7.3
Mutation Taster		=72/28	polymorphism

Other links and lift over

dbSNP: rs28359174; hg19: chrM-12811;