ENST00000361789.2:c.47A>G

Variant names:

• chrM-14793-A-G
• rs2853504
• ENST00000361789.2:c.47A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BA1

The ENST00000361789.2(MT-CYB):​c.47A>G​(p.His16Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H16Y) has been classified as Uncertain significance.

• Frequency: Mitomap GenBank: 𝑓 0.020 (AC: 1251)
• Consequence: MT-CYB ENST00000361789.2 missense
• Scores: Apogee2 Benign 0.025
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: 1.53
• Publications: 17 publications found

Genes affected

MT-CYB (HGNC:7427): (mitochondrially encoded cytochrome b) Predicted to enable metal ion binding activity. Predicted to be involved in several processes, including electron transport coupled proton transport; response to cobalamin; and response to glucagon. Located in mitochondrion. Implicated in ovarian carcinoma and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND6 (HGNC:7462): (mitochondrially encoded NADH dehydrogenase 6) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Predicted to be located in mitochondrial inner membrane. Implicated in Leber hereditary optic neuropathy; Leigh disease; and spinal muscular atrophy with lower extremity predominante 2B. [provided by Alliance of Genome Resources, Apr 2022]

TRNE (HGNC:7479): (mitochondrially encoded tRNA glutamic acid)

TRNE Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.024961192 < 0.5 .
• BP6: Variant M-14793-A-G is Benign according to our data. Variant chrM-14793-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 693766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: High frequency in mitomap database: 0.020499999

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361789.2. 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-CYB	ENST00000361789.2	TSL:6	c.47A>G	p.His16Arg	missense	Exon 1 of 1	ENSP00000354554.2	P00156
	MT-ND6	ENST00000361681.2	TSL:6	c.-120T>C		upstream_gene	N/A	ENSP00000354665.2	P03923
	MT-TE	ENST00000387459.1	TSL:6	n.-51T>C		upstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.020 AC: 1251

Gnomad homoplasmic AF: 0.031 AC: 1770 AN: 56383

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56383

Alfa AF: 0.0307 Hom.: 138

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Leigh syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.025
Hmtvar	Benign	0.17
AlphaMissense	Benign	0.096
PhyloP100		1.5
Mutation Taster		=82/18	polymorphism

Other links and lift over

dbSNP: rs2853504; hg19: chrM-14794;