rs2853497

Variant names:

• chrM-12007-G-A
• rs2853497
• unassigned_transcript_4811:c.1248G>A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

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: ND4 stop_gained
• Clinical Significance: Benign no assertion criteria provided B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -2.21

Genes affected

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]

TRNH (HGNC:7487): (mitochondrially encoded tRNA histidine)

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

ACMG classification

Verdict is Benign. Variant got -9 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.
• BA1: High frequency in mitomap database: 0.060100004

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND4	unassigned_transcript_4811	c.1248G>A	p.Trp416*	stop_gained	Exon 1 of 1
TRNH	unassigned_transcript_4812	c.-131G>A		upstream_gene_variant
TRNS2	unassigned_transcript_4813	c.-200G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

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

-

Genomics Division, Defence Institute of Physiology and Allied Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: case-control

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
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;