5-131182077-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_181705.4(LYRM7):c.92-152A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0658 in 658,528 control chromosomes in the GnomAD database, including 1,888 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (442 hom., cov: 32)
  • Exomes 𝑓: 0.067 (1446 hom.)
• Consequence: LYRM7 NM_181705.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.411

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:4912): (histidine triad nucleotide binding protein 1) This gene encodes a protein that hydrolyzes purine nucleotide phosphoramidates substrates, including AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester, and AMP-NH2. The encoded protein interacts with these substrates via a histidine triad motif. This gene is considered a tumor suppressor gene. In addition, mutations in this gene can cause autosomal recessive neuromyotonia and axonal neuropathy. There are several related pseudogenes on chromosome 7. Several transcript variants have been observed. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-131182077-A-G is Benign according to our data. Variant chr5-131182077-A-G is described in ClinVar as [Benign]. Clinvar id is 1273649.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYRM7	NM_181705.4	c.92-152A>G		intron_variant		ENST00000379380.9
LYRM7	NM_001293735.2	c.92-152A>G		intron_variant
LYRM7	NR_121658.2	n.168+1910A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYRM7	ENST00000379380.9	c.92-152A>G		intron_variant		1	NM_181705.4	P1
LYRM7	ENST00000507584.1	c.92-152A>G		intron_variant		2
LYRM7	ENST00000510516.5	c.91+1910A>G		intron_variant		2
HINT1	ENST00000506207.2	n.109-10344T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0613 AC: 9325 AN: 152178 Hom.: 440 Cov.: 32

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.0452

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0654

Gnomad OTH AF: 0.0698

GnomAD4 exome AF: 0.0672 AC: 34008 AN: 506232 Hom.: 1446 AF XY: 0.0701 AC XY: 18165 AN XY: 259298

Gnomad4 AFR exome AF: 0.00954

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.0575

Gnomad4 EAS exome AF: 0.0252

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.0880

Gnomad4 NFE exome AF: 0.0617

Gnomad4 OTH exome AF: 0.0631

GnomAD4 genome AF: 0.0614 AC: 9345 AN: 152296 Hom.: 442 Cov.: 32 AF XY: 0.0643 AC XY: 4789 AN XY: 74474

Gnomad4 AFR AF: 0.0149

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.0530

Gnomad4 EAS AF: 0.0457

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0815

Gnomad4 NFE AF: 0.0655

Gnomad4 OTH AF: 0.0714

Alfa AF: 0.0666 Hom.: 73

Bravo AF: 0.0634

Asia WGS AF: 0.104 AC: 359 AN: 3452

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.72
Dann	Benign	0.54

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: rs72803764; hg19: chr5-130517770; COSMIC: COSV65086284;