chr5-131182049-C-A

Position:

• chr5-131182049-C-A

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.92-180C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 152,150 control chromosomes in the GnomAD database, including 1,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.075 (1164 hom., cov: 31)
• Consequence: LYRM7 NM_181705.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.190

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=-0.92).
• BP6: Variant 5-131182049-C-A is Benign according to our data. Variant chr5-131182049-C-A is described in ClinVar as [Benign]. Clinvar id is 1230914.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYRM7	NM_181705.4	c.92-180C>A		intron_variant		ENST00000379380.9
LYRM7	NM_001293735.2	c.92-180C>A		intron_variant
LYRM7	NR_121658.2	n.168+1882C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYRM7	ENST00000379380.9	c.92-180C>A		intron_variant		1	NM_181705.4	P1
LYRM7	ENST00000507584.1	c.92-180C>A		intron_variant		2
LYRM7	ENST00000510516.5	c.91+1882C>A		intron_variant		2
HINT1	ENST00000506207.2	n.109-10316G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11364 AN: 152032 Hom.: 1163 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0342

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00851

Gnomad OTH AF: 0.0707

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0748 AC: 11381 AN: 152150 Hom.: 1164 Cov.: 31 AF XY: 0.0731 AC XY: 5442 AN XY: 74416

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.0405

Gnomad4 ASJ AF: 0.0265

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0344

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00849

Gnomad4 OTH AF: 0.0700

Alfa AF: 0.0464 Hom.: 90

Bravo AF: 0.0846

Asia WGS AF: 0.0400 AC: 137 AN: 3456

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 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.63
DANN	Benign	0.34

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: rs74935479; hg19: chr5-130517742;