5-131180313-T-G

Variant names:

• chr5-131180313-T-G
• rs60745433
• NM_181705.4:c.91+146T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_181705.4(LYRM7):​c.91+146T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0468 in 466,812 control chromosomes in the GnomAD database, including 1,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.074 (880 hom., cov: 30)
  • Exomes 𝑓: 0.033 (367 hom.)
• Consequence: LYRM7 NM_181705.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.980
• Publications: 2 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, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-131180313-T-G is Benign according to our data. Variant chr5-131180313-T-G is described in ClinVar as Benign. ClinVar VariationId is 676313.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 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+146T>G		intron	N/A	NP_859056.2	Q5U5X0
	LYRM7	NM_001293735.2		c.91+146T>G		intron	N/A	NP_001280664.1	D6RBV5
	LYRM7	NR_121658.2		n.168+146T>G		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+146T>G		intron	N/A	ENSP00000368688.4	Q5U5X0
	LYRM7	ENST00000855899.1		c.91+146T>G		intron	N/A	ENSP00000525958.1
	LYRM7	ENST00000931593.1		c.85+146T>G		intron	N/A	ENSP00000601652.1

Frequencies

GnomAD3 genomes AF: 0.0744 AC: 11312 AN: 152038 Hom.: 882 Cov.: 30

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.00773

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0300

Gnomad OTH AF: 0.0703

GnomAD4 exome AF: 0.0334 AC: 10524 AN: 314656 Hom.: 367 AF XY: 0.0331 AC XY: 5476 AN XY: 165370

African (AFR) AF: 0.185 AC: 1386 AN: 7496

American (AMR) AF: 0.0364 AC: 338 AN: 9292

Ashkenazi Jewish (ASJ) AF: 0.0751 AC: 766 AN: 10202

East Asian (EAS) AF: 0.000176 AC: 4 AN: 22764

South Asian (SAS) AF: 0.0147 AC: 285 AN: 19448

European-Finnish (FIN) AF: 0.0112 AC: 311 AN: 27746

Middle Eastern (MID) AF: 0.0918 AC: 156 AN: 1700

European-Non Finnish (NFE) AF: 0.0322 AC: 6363 AN: 197326

Other (OTH) AF: 0.0490 AC: 915 AN: 18682

GnomAD4 genome AF: 0.0745 AC: 11329 AN: 152156 Hom.: 880 Cov.: 30 AF XY: 0.0715 AC XY: 5319 AN XY: 74404

African (AFR) AF: 0.195 AC: 8079 AN: 41434

American (AMR) AF: 0.0406 AC: 620 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0761 AC: 264 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0126 AC: 61 AN: 4830

European-Finnish (FIN) AF: 0.00773 AC: 82 AN: 10610

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0301 AC: 2046 AN: 68020

Other (OTH) AF: 0.0695 AC: 147 AN: 2114

Alfa AF: 0.0272 Hom.: 35

Bravo AF: 0.0832

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

ClinVar submissions

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
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.4
DANN	Benign	0.73
PhyloP100		0.98
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: rs60745433; hg19: chr5-130516006;