5-131180382-CA-CAA

Variant names:

• chr5-131180382-C-CA
• rs60823900
• NM_181705.4:c.91+224dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_181705.4(LYRM7):​c.91+224dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 149,388 control chromosomes in the GnomAD database, including 249 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.031 (249 hom., cov: 30)
• Consequence: LYRM7 NM_181705.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.867
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 5-131180382-C-CA is Benign according to our data. Variant chr5-131180382-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1259123.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYRM7	NM_181705.4	MANE Select	c.91+224dupA		intron	N/A	NP_859056.2	Q5U5X0
	LYRM7	NM_001293735.2		c.91+224dupA		intron	N/A	NP_001280664.1	D6RBV5
	LYRM7	NR_121658.2		n.168+224dupA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYRM7	ENST00000379380.9	TSL:1 MANE Select	c.91+215_91+216insA		intron	N/A	ENSP00000368688.4	Q5U5X0
	LYRM7	ENST00000855899.1		c.91+215_91+216insA		intron	N/A	ENSP00000525958.1
	LYRM7	ENST00000931593.1		c.85+215_85+216insA		intron	N/A	ENSP00000601652.1

Frequencies

GnomAD3 genomes AF: 0.0306 AC: 4568 AN: 149272 Hom.: 247 Cov.: 30

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00873

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000447

Gnomad OTH AF: 0.0190

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

GnomAD4 genome AF: 0.0307 AC: 4591 AN: 149388 Hom.: 249 Cov.: 30 AF XY: 0.0295 AC XY: 2145 AN XY: 72806

African (AFR) AF: 0.106 AC: 4324 AN: 40818

American (AMR) AF: 0.0110 AC: 165 AN: 14996

Ashkenazi Jewish (ASJ) AF: 0.00873 AC: 30 AN: 3436

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.000211 AC: 1 AN: 4738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9864

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000447 AC: 30 AN: 67142

Other (OTH) AF: 0.0188 AC: 39 AN: 2078

Alfa AF: 0.00341 Hom.: 1

Bravo AF: 0.0346

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.87
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: rs60823900; hg19: chr5-130516075; COSMIC: COSV65086441;