M-15777-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000361789.2(MT-CYB):​c.1031G>C​(p.Ser344Thr) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S344N) has been classified as Likely benign.

• Frequency: Mitomap GenBank: 𝑓 0.00050 (AC: 32)
• Consequence: MT-CYB ENST00000361789.2 missense
• Scores: Apogee2 Benign 0.011
• Clinical Significance: Benign criteria provided, single submitter B:1 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 -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.011060337 < 0.5 .
• BP6: Variant M-15777-G-C is Benign according to our data. Variant chrM-15777-G-C is described in ClinVar as Benign. ClinVar VariationId is 693950.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 138

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTB	unassigned_transcript_4818	c.1031G>C	p.Ser344Thr	missense_variant	Exon 1 of 1
TRNT	unassigned_transcript_4819	c.-111G>C		upstream_gene_variant
TRNP	unassigned_transcript_4820	c.*179C>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CYB	ENST00000361789.2	c.1031G>C	p.Ser344Thr	missense_variant	Exon 1 of 1	6		ENSP00000354554.2
MT-TT	ENST00000387460.2	n.-111G>C		upstream_gene_variant		6
MT-TP	ENST00000387461.2	n.*179C>G		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.00050 AC: 32

Gnomad homoplasmic AF: 0.0024 AC: 138 AN: 56432

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56432

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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>C (YP_003024038.1:p.Ser344Thr) 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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.011
Hmtvar	Pathogenic	0.40
AlphaMissense	Benign	0.092
PhyloP100		4.7

Other links and lift over

dbSNP: rs879182710; hg19: chrM-15778;