chr5-131180118-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_181705.4(LYRM7):c.42G>A(p.Leu14Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 1,611,338 control chromosomes in the GnomAD database, including 1,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 95 hom., cov: 30)

Exomes 𝑓: 0.039 ( 1341 hom. )

Consequence

LYRM7
NM_181705.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.07

Variant links:

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]

LYRM7 links:

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]

HINT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 5-131180118-G-A is Benign according to our data. Variant chr5-131180118-G-A is described in ClinVar as [Benign]. Clinvar id is 380079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-131180118-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.07 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0313 (4764/152112) while in subpopulation NFE AF= 0.0456 (3102/68004). AF 95% confidence interval is 0.0443. There are 95 homozygotes in gnomad4. There are 2330 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 95 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYRM7	NM_181705.4 link	c.42G>A	p.Leu14Leu	synonymous_variant	Exon 2 of 5	ENST00000379380.9	NP_859056.2	Q5U5X0
LYRM7	NM_001293735.2 link	c.42G>A	p.Leu14Leu	synonymous_variant	Exon 2 of 4		NP_001280664.1	D6RBV5
LYRM7	NR_121658.2 link	n.119G>A		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LYRM7	ENST00000379380.9 link	c.42G>A	p.Leu14Leu	synonymous_variant	Exon 2 of 5	1	NM_181705.4	ENSP00000368688.4	Q5U5X0
LYRM7	ENST00000507584.1 link	c.42G>A	p.Leu14Leu	synonymous_variant	Exon 2 of 4	2		ENSP00000423991.1	D6RBV5
LYRM7	ENST00000510516.5 link	c.42G>A	p.Leu14Leu	synonymous_variant	Exon 2 of 3	2		ENSP00000423283.1	D6R994
HINT1	ENST00000506207.2 link	n.109-8385C>T		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.0313

AC:

4764

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00820

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0207

Gnomad ASJ

AF:

0.0277

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0220

Gnomad FIN

AF:

0.0683

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.0456

Gnomad OTH

AF:

0.0321

GnomAD3 exomes

AF:

0.0338

AC:

8461

AN:

250584

Hom.:

234

AF XY:

0.0349

AC XY:

4723

AN XY:

135488

show subpopulations

Gnomad AFR exome

AF:

0.00598

Gnomad AMR exome

AF:

0.0135

Gnomad ASJ exome

AF:

0.0286

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0220

Gnomad FIN exome

AF:

0.0759

Gnomad NFE exome

AF:

0.0449

Gnomad OTH exome

AF:

0.0331

GnomAD4 exome

AF:

0.0391

AC:

57011

AN:

1459226

Hom.:

1341

Cov.:

AF XY:

0.0389

AC XY:

28227

AN XY:

726062

show subpopulations

Gnomad4 AFR exome

AF:

0.00577

Gnomad4 AMR exome

AF:

0.0143

Gnomad4 ASJ exome

AF:

0.0285

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0224

Gnomad4 FIN exome

AF:

0.0733

Gnomad4 NFE exome

AF:

0.0428

Gnomad4 OTH exome

AF:

0.0328

GnomAD4 genome

AF:

0.0313

AC:

4764

AN:

152112

Hom.:

Cov.:

AF XY:

0.0313

AC XY:

2330

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00817

Gnomad4 AMR

AF:

0.0207

Gnomad4 ASJ

AF:

0.0277

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0220

Gnomad4 FIN

AF:

0.0683

Gnomad4 NFE

AF:

0.0456

Gnomad4 OTH

AF:

0.0318

Alfa

AF:

0.0391

Hom.:

Bravo

AF:

0.0258

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0425

EpiControl

AF:

0.0414

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 22, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Feb 04, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

9.4

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over