5-131180675-A-C

Variant names:

• chr5-131180675-A-C
• rs10052199
• NM_181705.4:c.91+508A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

HINT1 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Gamstorp-Wohlfart syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181705.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYRM7	NM_181705.4	MANE Select	c.91+508A>C		intron	N/A	NP_859056.2
	LYRM7	NM_001293735.2		c.91+508A>C		intron	N/A	NP_001280664.1
	LYRM7	NR_121658.2		n.168+508A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYRM7	ENST00000379380.9	TSL:1 MANE Select	c.91+508A>C		intron	N/A	ENSP00000368688.4
	LYRM7	ENST00000507584.1	TSL:2	c.91+508A>C		intron	N/A	ENSP00000423991.1
	LYRM7	ENST00000510516.5	TSL:2	c.91+508A>C		intron	N/A	ENSP00000423283.1

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

African (AFR) AF: 0.710 AC: 29455 AN: 41466

American (AMR) AF: 0.192 AC: 2931 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 529 AN: 3468

East Asian (EAS) AF: 0.117 AC: 608 AN: 5178

South Asian (SAS) AF: 0.185 AC: 891 AN: 4824

European-Finnish (FIN) AF: 0.162 AC: 1713 AN: 10572

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10667 AN: 67984

Other (OTH) AF: 0.275 AC: 580 AN: 2110

Alfa AF: 0.210 Hom.: 6656

Bravo AF: 0.331

Asia WGS AF: 0.208 AC: 727 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10052199; hg19: chr5-130516368;