5-131180127-C-T

Position:

• chr5-131180127-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 2P and 15B. PM2 BP4_Moderate BP6_Very_Strong BP7 BS1

The NM_181705.4(LYRM7):​c.51C>T​(p.Thr17Thr) 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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.876

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: 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: Synonymous conserved (PhyloP=-0.876 with no splicing effect.
• BS1: 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	Protein	UniProt
LYRM7	NM_181705.4	c.51C>T	p.Thr17Thr	synonymous_variant	2/5	ENST00000379380.9	NP_859056.2
LYRM7	NM_001293735.2	c.51C>T	p.Thr17Thr	synonymous_variant	2/4		NP_001280664.1
LYRM7	NR_121658.2	n.128C>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYRM7	ENST00000379380.9	c.51C>T	p.Thr17Thr	synonymous_variant	2/5	1	NM_181705.4	ENSP00000368688.4
LYRM7	ENST00000507584.1	c.51C>T	p.Thr17Thr	synonymous_variant	2/4	2		ENSP00000423991.1
LYRM7	ENST00000510516.5	c.51C>T	p.Thr17Thr	synonymous_variant	2/3	2		ENSP00000423283.1
HINT1	ENST00000506207.2	n.109-8394G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.000362 AC: 55 AN: 152038 Hom.: 0 Cov.: 30

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

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

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 AF: 0.000362 AC: 55 AN: 152038 Hom.: 0 Cov.: 30 AF XY: 0.000377 AC XY: 28 AN XY: 74264

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

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 27, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 01, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	LYRM7: BP4, BP7 -

LYRM7-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 07, 2019

This 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

Other links and lift over

dbSNP: rs144249672; hg19: chr5-130515820;