5-131171048-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_181705.4(LYRM7):c.18+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,527,368 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 101 hom. )

Consequence

LYRM7
NM_181705.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0980

Publications

4 publications found

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 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

HINT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 5-131171048-C-T is Benign according to our data. Variant chr5-131171048-C-T is described in ClinVar as Benign. ClinVar VariationId is 506355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0608 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LYRM7	NM_181705.4	MANE Select	c.18+10C>T	intron	N/A	NP_859056.2	Q5U5X0
LYRM7	NM_001293735.2		c.18+10C>T	intron	N/A	NP_001280664.1	D6RBV5
LYRM7	NR_121658.2		n.95+10C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LYRM7	ENST00000379380.9	TSL:1 MANE Select	c.18+10C>T	intron	N/A	ENSP00000368688.4	Q5U5X0
LYRM7	ENST00000855899.1		c.18+10C>T	intron	N/A	ENSP00000525958.1
LYRM7	ENST00000931593.1		c.12+16C>T	intron	N/A	ENSP00000601652.1

Frequencies

GnomAD3 genomes

AF:

0.00266

AC:

405

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000525

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0670

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00447

AC:

718

AN:

160706

AF XY:

0.00386

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000135

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0723

Gnomad FIN exome

AF:

0.00202

Gnomad NFE exome

AF:

0.000311

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.00224

AC:

3074

AN:

1375266

Hom.:

101

Cov.:

AF XY:

0.00223

AC XY:

1519

AN XY:

681846

show subpopulations

African (AFR)

AF:

0.0000361

AC:

AN:

27682

American (AMR)

AF:

0.000119

AC:

AN:

25128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23102

East Asian (EAS)

AF:

0.0762

AC:

2501

AN:

32816

South Asian (SAS)

AF:

0.00139

AC:

101

AN:

72580

European-Finnish (FIN)

AF:

0.00227

AC:

118

AN:

51918

Middle Eastern (MID)

AF:

0.000730

AC:

AN:

5480

European-Non Finnish (NFE)

AF:

0.000110

AC:

119

AN:

1079786

Other (OTH)

AF:

0.00400

AC:

227

AN:

56774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

146

293

439

586

732

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00264

AC:

401

AN:

152102

Hom.:

Cov.:

AF XY:

0.00296

AC XY:

220

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41460

American (AMR)

AF:

0.000524

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.0666

AC:

344

AN:

5166

South Asian (SAS)

AF:

0.00332

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68002

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000828

Hom.:

Bravo

AF:

0.00278

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.9

(source)

DANN

Benign

0.91

PhyloP100

-0.098

PromoterAI

-0.025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over