chr5-131179944-A-T

Position:

• chr5-131179944-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:):

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 GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYRM7	NM_181705.4	c.19-151A>T		intron_variant		ENST00000379380.9	NP_859056.2
LYRM7	NM_001293735.2	c.19-151A>T		intron_variant			NP_001280664.1
LYRM7	NR_121658.2	n.96-151A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYRM7	ENST00000379380.9	c.19-151A>T		intron_variant		1	NM_181705.4	ENSP00000368688.4
LYRM7	ENST00000507584.1	c.19-151A>T		intron_variant		2		ENSP00000423991.1
LYRM7	ENST00000510516.5	c.19-151A>T		intron_variant		2		ENSP00000423283.1
HINT1	ENST00000506207.2	n.109-8211T>A		intron_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

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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;