chr5-131171033-G-C

Position:

• chr5-131171033-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181705.4(LYRM7):​c.13G>C​(p.Val5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,382,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: LYRM7 NM_181705.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04101792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYRM7	NM_181705.4	c.13G>C	p.Val5Leu	missense_variant	1/5	ENST00000379380.9	NP_859056.2
LYRM7	NM_001293735.2	c.13G>C	p.Val5Leu	missense_variant	1/4		NP_001280664.1
LYRM7	NR_121658.2	n.90G>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYRM7	ENST00000379380.9	c.13G>C	p.Val5Leu	missense_variant	1/5	1	NM_181705.4	ENSP00000368688.4
LYRM7	ENST00000507584.1	c.13G>C	p.Val5Leu	missense_variant	1/4	2		ENSP00000423991.1
LYRM7	ENST00000510516.5	c.13G>C	p.Val5Leu	missense_variant	1/3	2		ENSP00000423283.1
HINT1	ENST00000506207.2	n.236+573C>G		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1382078 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 685566

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.24e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2022

The c.13G>C (p.V5L) alteration is located in exon 1 (coding exon 1) of the LYRM7 gene. This alteration results from a G to C substitution at nucleotide position 13, causing the valine (V) at amino acid position 5 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.64
DEOGEN2	Benign	0.0068	T;.;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.48	T;T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.041	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.8	N;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.92	N;N;N
REVEL	Benign	0.089
Sift	Benign	0.72	T;D;T
Sift4G	Benign	0.61	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.084
MutPred		0.25		Loss of methylation at K6 (P = 0.039);Loss of methylation at K6 (P = 0.039);Loss of methylation at K6 (P = 0.039);
MVP		0.030
MPC		0.040
ClinPred		0.067	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.094
gMVP		0.12

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

Publications

LitVar

Other links and lift over

dbSNP: rs1368424392; hg19: chr5-130506726;