M-961-T-G

Variant names:

• chrM-961-T-G
• rs3888511
• ENST00000389680.2:n.314T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The ENST00000000000(RNR1):​n.314T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0037 (AC: 226)
• Consequence: RNR1 ENST00000000000 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts P:1 U:1 B:2 DEAF+-possibly-LVNC-associated,DEAF-/-AD-associated-/-intellectual-disability,Possibly-DEAF-associated
• Conservation: PhyloP100: -7.53
• Publications: 13 publications found

Genes affected

MT-RNR1 (HGNC:7470): (mitochondrially encoded 12S RNA) Enables DNA binding activity and DNA-binding transcription factor binding activity. Involved in several processes, including osteoblast proliferation; regulation of carbohydrate utilization; and regulation of phosphate metabolic process. Located in extracellular space; mitochondrion; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MT-RNR1 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP6: Variant M-961-T-G is Benign according to our data. Variant chrM-961-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 9633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 442

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000389680.2. 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-RNR1	ENST00000389680.2	TSL:6	n.314T>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

Mitomap GenBank AF: 0.0037 AC: 226

Gnomad homoplasmic AF: 0.0078 AC: 442 AN: 56432

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56432

Mitomap

Disease(s): DEAF+-possibly-LVNC-associated,DEAF-/-AD-associated-/-intellectual-disability,Possibly-DEAF-associated

Status: Unclear,Unclear,Unclear

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
1	1	-	Mitochondrial non-syndromic sensorineural hearing loss (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-7.5

Other links and lift over

dbSNP: rs3888511; hg19: chrM-963;