rs41518645

chrM-15257-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PS1_Moderate BP4 BP6_Moderate BA1

The ENST00000361789.2(MT-CYB):c.511G>A(p.Asp171Asn) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

• Frequency: Mitomap GenBank: 𝑓 0.015 (AC: 934)
• Consequence: MT-CYB ENST00000361789.2 missense
• Scores: Apogee2 Benign 0.17
• Clinical Significance: Benign criteria provided, single submitter P:1 U:1 B:1 LHON
• Conservation: PhyloP100: 6.10

Genes affected

CYTB (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• PS1: Transcript ENST00000361789.2 (MT-CYB) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
• BP4: Apogee2 supports a benign effect, 0.17390026 < 0.5 .
• BP6: Variant M-15257-G-A is Benign according to our data. Variant chrM-15257-G-A is described in ClinVar as [Benign]. Clinvar id is 9674.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: High frequency in mitomap database: 0.0153

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYTB	CYTB.1	c.511G>A	p.Asp171Asn	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-CYB	ENST00000361789.2	c.511G>A	p.Asp171Asn	missense_variant	1/1			P1

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap GenBank AF: 0.015 AC: 934

Gnomad homoplasmic AF: 0.013 AC: 719 AN: 56424

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56424

Alfa AF: 0.0182 Hom.: 714

Mitomap

LHON

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Uncertain:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leber optic atrophy Pathogenic:1 Uncertain:1

Uncertain significance, no assertion criteria provided	curation	GeneReviews	Sep 19, 2013	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Aug 01, 1996	- -

Leigh syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Oct 17, 2019

The NC_012920.1:m.15257G>A (YP_003024038.1:p.Asp171Asn) 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: BA1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.17
Hmtvar	Benign	0.24
AlphaMissense	Benign	0.12

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs41518645; hg19: chrM-15258; COSMIC: COSV62378578; COSMIC: COSV62378578;