rs28718242

Positions:

• chrM-11899-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP6_Moderate BP7 BS1 BS2

The ENST00000361381.2(MT-ND4):​c.1140T>C​(p.Ser380=) 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 0.0086 (AC: 528)
• Consequence: MT-ND4 ENST00000361381.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -8.87

Genes affected

MT-ND4 (HGNC:7459): (mitochondrially encoded NADH dehydrogenase 4) 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; Parkinson's disease; macular degeneration; and schizophrenia. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP6: Variant M-11899-T-C is Benign according to our data. Variant chrM-11899-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 235318.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-8.87 with no splicing effect.
• BS1: High frequency in mitomap database: 0.0086
• BS2: High AC in GnomadMitoHomoplasmic at 585

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-ND4	ENST00000361381.2	c.1140T>C	p.Ser380=	synonymous_variant	1/1			P1

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0086 AC: 528

Gnomad homoplasmic AF: 0.010 AC: 585 AN: 56425

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56425

Alfa AF: 0.00352 Hom.: 131

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Aug 12, 2015

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28718242; hg19: chrM-11900;