5-131179944-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_181705.4(LYRM7):c.19-151A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00911 in 453,152 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0089 (17 hom., cov: 30)
  • Exomes 𝑓: 0.0092 (9 hom.)
• Consequence: LYRM7 NM_181705.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.51

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 5-131179944-A-T is Benign according to our data. Variant chr5-131179944-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1209485.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00887 (1330/149926) while in subpopulation NFE AF= 0.0127 (853/67308). AF 95% confidence interval is 0.012. There are 17 homozygotes in gnomad4. There are 681 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYRM7	NM_181705.4	c.19-151A>T		intron_variant		ENST00000379380.9
LYRM7	NM_001293735.2	c.19-151A>T		intron_variant
LYRM7	NR_121658.2	n.96-151A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYRM7	ENST00000379380.9	c.19-151A>T		intron_variant		1	NM_181705.4	P1
LYRM7	ENST00000507584.1	c.19-151A>T		intron_variant		2
LYRM7	ENST00000510516.5	c.19-151A>T		intron_variant		2
HINT1	ENST00000506207.2	n.109-8211T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00888 AC: 1330 AN: 149816 Hom.: 17 Cov.: 30

Gnomad AFR AF: 0.00250

Gnomad AMI AF: 0.0476

Gnomad AMR AF: 0.00599

Gnomad ASJ AF: 0.00786

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.00234

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.0127

Gnomad OTH AF: 0.0102

GnomAD4 exome AF: 0.00922 AC: 2797 AN: 303226 Hom.: 9 AF XY: 0.00881 AC XY: 1440 AN XY: 163464

Gnomad4 AFR exome AF: 0.00382

Gnomad4 AMR exome AF: 0.00623

Gnomad4 ASJ exome AF: 0.0100

Gnomad4 EAS exome AF: 0.000320

Gnomad4 SAS exome AF: 0.00213

Gnomad4 FIN exome AF: 0.0117

Gnomad4 NFE exome AF: 0.0116

Gnomad4 OTH exome AF: 0.00802

GnomAD4 genome AF: 0.00887 AC: 1330 AN: 149926 Hom.: 17 Cov.: 30 AF XY: 0.00932 AC XY: 681 AN XY: 73098

Gnomad4 AFR AF: 0.00250

Gnomad4 AMR AF: 0.00599

Gnomad4 ASJ AF: 0.00786

Gnomad4 EAS AF: 0.000390

Gnomad4 SAS AF: 0.00234

Gnomad4 FIN AF: 0.0176

Gnomad4 NFE AF: 0.0127

Gnomad4 OTH AF: 0.0101

Alfa AF: 0.0104 Hom.: 0

Bravo AF: 0.00764

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.27
Dann	Benign	0.49

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: rs183113457; hg19: chr5-130515637;