rs869025602

Positions:

• chr5-131187113-A-AG

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_181705.4(LYRM7):​c.244+5dupG variant causes a splice region, intron change. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LYRM7 NM_181705.4 splice_region, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.97

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-131187113-A-AG is Pathogenic according to our data. Variant chr5-131187113-A-AG is described in ClinVar as [Pathogenic]. Clinvar id is 223134.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.244+5dupG		splice_region_variant, intron_variant		ENST00000379380.9	NP_859056.2
LYRM7	NM_001293735.2	c.162+4815dupG		intron_variant			NP_001280664.1
LYRM7	NR_121658.2	n.168+6947dupG		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYRM7	ENST00000379380.9	c.244+5dupG		splice_region_variant, intron_variant		1	NM_181705.4	ENSP00000368688.4
LYRM7	ENST00000507584.1	c.162+4815dupG		intron_variant		2		ENSP00000423991.1
LYRM7	ENST00000510516.5	c.91+6947dupG		intron_variant		2		ENSP00000423283.1
HINT1	ENST00000506207.2	n.109-15381dupC		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 20

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

Mar 02, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.76		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.31		Position offset: 0
DS_DL_spliceai		0.76		Position offset: -4

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

Publications

LitVar

Other links and lift over

dbSNP: rs869025602; hg19: chr5-130522806;