rs199951903

Variant names:

• chrM-15497-G-A
• rs199951903
• ENST00000361789.2:c.751G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BS1 BS2

The ENST00000361789.2(MT-CYB):​c.751G>A​(p.Gly251Ser) variant causes a missense change. In-silico tool predicts 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. G251D) has been classified as Uncertain significance.

• Frequency: Mitomap GenBank: 𝑓 0.0055 (AC: 338)
• Consequence: MT-CYB ENST00000361789.2 missense
• Scores: Apogee2 Benign 0.053
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 O:1 EXIT-/-Obesity
• Conservation: PhyloP100: 5.32
• Publications: 16 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-CYB Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial complex III deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Apogee2 supports a benign effect, 0.052852184 < 0.5 .
• BP6: Variant M-15497-G-A is Benign according to our data. Variant chrM-15497-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 9687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: High frequency in mitomap database: 0.0055
• BS2: High AC in GnomadMitoHomoplasmic at 218

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.751G>A	p.Gly251Ser	missense	Exon 1 of 1	ENSP00000354554.2	P00156

Frequencies

Mitomap GenBank AF: 0.0055 AC: 338

Gnomad homoplasmic AF: 0.0039 AC: 218 AN: 56417

Gnomad heteroplasmic AF: 0.000089 AC: 5 AN: 56417

Alfa AF: 0.00303 Hom.: 38

Mitomap

Disease(s): EXIT-/-Obesity

Status: Reported

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Leigh syndrome (1)
-	-	1	not provided (1)
-	-	-	Obesity (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.053
Hmtvar	Benign	0.22
AlphaMissense	Benign	0.10
PhyloP100		5.3
Mutation Taster		=36/64	disease causing

Other links and lift over

dbSNP: rs199951903; hg19: chrM-15498;