5-131180313-T-G

Position:

• chr5-131180313-T-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYRM7	NM_181705.4	c.91+146T>G		intron_variant		ENST00000379380.9	NP_859056.2
LYRM7	NM_001293735.2	c.91+146T>G		intron_variant			NP_001280664.1
LYRM7	NR_121658.2	n.168+146T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYRM7	ENST00000379380.9	c.91+146T>G		intron_variant		1	NM_181705.4	ENSP00000368688.4
LYRM7	ENST00000507584.1	c.91+146T>G		intron_variant		2		ENSP00000423991.1
LYRM7	ENST00000510516.5	c.91+146T>G		intron_variant		2		ENSP00000423283.1
HINT1	ENST00000506207.2	n.109-8580A>C		intron_variant		5

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

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.0364

Gnomad4 ASJ exome AF: 0.0751

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0147

Gnomad4 FIN exome AF: 0.0112

Gnomad4 NFE exome AF: 0.0322

Gnomad4 OTH exome AF: 0.0490

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

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.0406

Gnomad4 ASJ AF: 0.0761

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.00773

Gnomad4 NFE AF: 0.0301

Gnomad4 OTH AF: 0.0695

Alfa AF: 0.0194 Hom.: 17

Bravo AF: 0.0832

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.4
DANN	Benign	0.73

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: rs60745433; hg19: chr5-130516006;