M-15777-G-A

Variant names:

• chrM-15777-G-A
• rs879182710
• ENST00000361789.2:c.1031G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4 BP6_Very_Strong BS2

The ENST00000361789.2(MT-CYB):​c.1031G>A​(p.Ser344Asn) 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. S344T) has been classified as Benign.

• Frequency: Mitomap GenBank: 𝑓 0.0018 (AC: 112)
• Consequence: MT-CYB ENST00000361789.2 missense
• Scores: Apogee2 Benign 0.015
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: 4.74
• Publications: 2 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]

TRNT (HGNC:7499): (mitochondrially encoded tRNA threonine)

TRNP (HGNC:7494): (mitochondrially encoded tRNA proline)

TRNP Gene-Disease associations (from GenCC):

• MERRF syndrome

  Inheritance: Mitochondrial Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.014891338 < 0.5 .
• BP6: Variant M-15777-G-A is Benign according to our data. Variant chrM-15777-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 377195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 38

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTB	unassigned_transcript_4818	c.1031G>A	p.Ser344Asn	missense_variant	Exon 1 of 1
TRNT	unassigned_transcript_4819	c.-111G>A		upstream_gene_variant
TRNP	unassigned_transcript_4820	c.*179C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CYB	ENST00000361789.2	c.1031G>A	p.Ser344Asn	missense_variant	Exon 1 of 1	6		ENSP00000354554.2
MT-TT	ENST00000387460.2	n.-111G>A		upstream_gene_variant		6
MT-TP	ENST00000387461.2	n.*179C>T		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.0018 AC: 112

Gnomad homoplasmic AF: 0.00067 AC: 38 AN: 56414

Gnomad heteroplasmic AF: 0.00014 AC: 8 AN: 56414

Alfa AF: 0.000891 Hom.: 4

Mitomap

No disease associated.

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leigh syndrome Benign:1

Oct 17, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.15777G>A (YP_003024038.1:p.Ser344Asn) variant in MTCYB gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BS2, BP4 -

not provided Benign:1

Jan 06, 2017

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.015
Hmtvar	Benign	0.19
AlphaMissense	Benign	0.10
PhyloP100		4.7
Mutation Taster		=15/185	disease causing

Other links and lift over

dbSNP: rs879182710; hg19: chrM-15778; COSMIC: COSV104670485; COSMIC: COSV104670485;