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5-131180127-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 2P and 15B. PM2BP4_ModerateBP6_Very_StrongBP7BS1

The NM_181705.4(LYRM7):c.51C>T(p.Thr17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000582 in 1,612,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00061 ( 0 hom. )

Consequence

LYRM7
NM_181705.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.876
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-131180127-C-T is Benign according to our data. Variant chr5-131180127-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 390001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.876 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000362 (55/152038) while in subpopulation NFE AF= 0.000721 (49/67996). AF 95% confidence interval is 0.00056. There are 0 homozygotes in gnomad4. There are 28 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LYRM7NM_181705.4 linkuse as main transcriptc.51C>T p.Thr17= synonymous_variant 2/5 ENST00000379380.9
LYRM7NM_001293735.2 linkuse as main transcriptc.51C>T p.Thr17= synonymous_variant 2/4
LYRM7NR_121658.2 linkuse as main transcriptn.128C>T non_coding_transcript_exon_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LYRM7ENST00000379380.9 linkuse as main transcriptc.51C>T p.Thr17= synonymous_variant 2/51 NM_181705.4 P1
LYRM7ENST00000507584.1 linkuse as main transcriptc.51C>T p.Thr17= synonymous_variant 2/42
LYRM7ENST00000510516.5 linkuse as main transcriptc.51C>T p.Thr17= synonymous_variant 2/32
HINT1ENST00000506207.2 linkuse as main transcriptn.109-8394G>A intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000362
AC:
55
AN:
152038
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000967
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000944
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000721
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000331
AC:
83
AN:
250796
Hom.:
0
AF XY:
0.000354
AC XY:
48
AN XY:
135584
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000324
Gnomad NFE exome
AF:
0.000599
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000605
AC:
884
AN:
1460748
Hom.:
0
Cov.:
28
AF XY:
0.000559
AC XY:
406
AN XY:
726746
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000150
Gnomad4 NFE exome
AF:
0.000767
Gnomad4 OTH exome
AF:
0.000348
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000362
AC:
55
AN:
152038
Hom.:
0
Cov.:
30
AF XY:
0.000377
AC XY:
28
AN XY:
74264
show subpopulations
Gnomad4 AFR
AF:
0.0000967
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000944
Gnomad4 NFE
AF:
0.000721
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000703
Hom.:
1
Bravo
AF:
0.000382
EpiCase
AF:
0.000655
EpiControl
AF:
0.000831

ClinVar

Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Likely benign, criteria provided, single submitterclinical testingInvitaeNov 27, 2023- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2024LYRM7: BP4, BP7 -
Likely benign, criteria provided, single submitterclinical testingGeneDxOct 01, 2020- -
LYRM7-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMay 07, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
Cadd
Benign
8.5
Dann
Benign
0.65
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs144249672; hg19: chr5-130515820; API