5-131180675-A-C

Position:

• chr5-131180675-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181705.4(LYRM7):​c.91+508A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,086 control chromosomes in the GnomAD database, including 12,146 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (12146 hom., cov: 30)
• Consequence: LYRM7 NM_181705.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYRM7	NM_181705.4	c.91+508A>C		intron_variant		ENST00000379380.9	NP_859056.2
LYRM7	NM_001293735.2	c.91+508A>C		intron_variant			NP_001280664.1
LYRM7	NR_121658.2	n.168+508A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYRM7	ENST00000379380.9	c.91+508A>C		intron_variant		1	NM_181705.4	ENSP00000368688.4
LYRM7	ENST00000507584.1	c.91+508A>C		intron_variant		2		ENSP00000423991.1
LYRM7	ENST00000510516.5	c.91+508A>C		intron_variant		2		ENSP00000423283.1
HINT1	ENST00000506207.2	n.109-8942T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47420 AN: 151968 Hom.: 12106 Cov.: 30

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.312 AC: 47506 AN: 152086 Hom.: 12146 Cov.: 30 AF XY: 0.306 AC XY: 22744 AN XY: 74348

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.275

Alfa AF: 0.190 Hom.: 3947

Bravo AF: 0.331

Asia WGS AF: 0.208 AC: 727 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10052199; hg19: chr5-130516368;