rs2853497

Positions:

• chrM-12007-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6 BP7 BA1

The ENST00000361381.2(MT-ND4):​c.1248G>A​(p.Trp416=) 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 Benign (no stars).

• Frequency: Mitomap GenBank: 𝑓 0.060 (AC: 3672)
• Consequence: MT-ND4 ENST00000361381.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -2.21

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 -10 ACMG points.

• BP6: Variant M-12007-G-A is Benign according to our data. Variant chrM-12007-G-A is described in ClinVar as [Benign]. Clinvar id is 3027422.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.21 with no splicing effect.
• BA1: High frequency in mitomap database: 0.060100004

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.1248G>A	p.Trp416=	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: 0.060 AC: 3672

Gnomad homoplasmic AF: 0.071 AC: 4017 AN: 56402

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56402

Alfa AF: 0.0224 Hom.: 188

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Venous thromboembolism Benign:1

Benign, no assertion criteria provided

case-control

Genomics Division, Defence Institute of Physiology and Allied Sciences

-

Three age and sex matched study groups were taken and whole exome sequencing was performed. 1. Healthy Subjects (n=19) 2. Sea Level Venous Thromboembolism (n=15) 3. High Altitude Venous Thromboembolism (n=6) This variant is benign in nature. After analysis we found frequency of rs2853497 in only high altitude induced Thromboembolism study groups. However, this SNP was absent in Healthy Subjects and sea level Thromboembolism study groups. First time it is being reported that there is association of rs2853497with Venous Thromboembolism. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.42	T
MutationTaster	Benign	1.0	N
GERP RS		-6.6

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2853497; hg19: chrM-12008;