chr5-131171048-C-T

Variant names:

• chr5-131171048-C-T
• rs2285978
• NM_181705.4:c.18+10C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0980

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYRM7	NM_181705.4	c.18+10C>T		intron_variant	Intron 1 of 4	ENST00000379380.9	NP_859056.2
LYRM7	NM_001293735.2	c.18+10C>T		intron_variant	Intron 1 of 3		NP_001280664.1
LYRM7	NR_121658.2	n.95+10C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYRM7	ENST00000379380.9	c.18+10C>T		intron_variant	Intron 1 of 4	1	NM_181705.4	ENSP00000368688.4
LYRM7	ENST00000507584.1	c.18+10C>T		intron_variant	Intron 1 of 3	2		ENSP00000423991.1
LYRM7	ENST00000510516.5	c.18+10C>T		intron_variant	Intron 1 of 2	2		ENSP00000423283.1
HINT1	ENST00000506207.2	n.236+558G>A		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.00266 AC: 405 AN: 151984 Hom.: 13 Cov.: 32

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

GnomAD3 exomes AF: 0.00447 AC: 718 AN: 160706 Hom.: 32 AF XY: 0.00386 AC XY: 343 AN XY: 88926

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 SAS exome AF: 0.00108

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.: 30 AF XY: 0.00223 AC XY: 1519 AN XY: 681846

Gnomad4 AFR exome AF: 0.0000361

Gnomad4 AMR exome AF: 0.000119

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0762

Gnomad4 SAS exome AF: 0.00139

Gnomad4 FIN exome AF: 0.00227

Gnomad4 NFE exome AF: 0.000110

Gnomad4 OTH exome AF: 0.00400

GnomAD4 genome AF: 0.00264 AC: 401 AN: 152102 Hom.: 13 Cov.: 32 AF XY: 0.00296 AC XY: 220 AN XY: 74360

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.000524

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0666

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000828 Hom.: 0

Bravo AF: 0.00278

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jun 13, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.9
DANN	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs2285978; hg19: chr5-130506741;