rs869025603

Positions:

• chr5-131187053-A-AATT

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_181705.4(LYRM7):​c.193_195dupTTA​(p.Leu66dup) variant causes a conservative inframe insertion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LYRM7 NM_181705.4 conservative_inframe_insertion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.12

Genes affected

LYRM7 (HGNC:28072): (LYR motif containing 7) Inner mitochondrial membrane complex III (CIII) is the main enzyme complex in the mitochondrial respiratory chain, and Rieske Fe-S protein (UQCRFS1) is the last catalytic subunit added to the complex. The protein encoded by this gene is a nuclear-encoded mitochondrial matrix protein that stabilizes UQCRFS1 and chaperones it to the CIII complex. Defects in this gene are a cause of mitochondrial complex III deficiency, nuclear type 8. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

HINT1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_181705.4. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 5-131187053-A-AATT is Pathogenic according to our data. Variant chr5-131187053-A-AATT is described in ClinVar as [Pathogenic]. Clinvar id is 223135.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYRM7	NM_181705.4	c.193_195dupTTA	p.Leu66dup	conservative_inframe_insertion	4/5	ENST00000379380.9	NP_859056.2
LYRM7	NM_001293735.2	c.162+4759_162+4761dupTTA		intron_variant			NP_001280664.1
LYRM7	NR_121658.2	n.168+6891_168+6893dupTTA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYRM7	ENST00000379380.9	c.193_195dupTTA	p.Leu66dup	conservative_inframe_insertion	4/5	1	NM_181705.4	ENSP00000368688.4
LYRM7	ENST00000507584.1	c.162+4759_162+4761dupTTA		intron_variant		2		ENSP00000423991.1
LYRM7	ENST00000510516.5	c.91+6891_91+6893dupTTA		intron_variant		2		ENSP00000423283.1
HINT1	ENST00000506207.2	n.109-15323_109-15321dupAAT		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Mitochondrial complex III deficiency nuclear type 8 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs869025603; hg19: chr5-130522746;