Genetic Variant LYRM4:c.86+69G>C (chr6-5260579-C-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_020408.6(LYRM4):c.86+69G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,266,048 control chromosomes in the GnomAD database, including 51,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.39 ( 15378 hom., cov: 32)

Exomes 𝑓: 0.19 ( 36522 hom. )

Consequence

LYRM4
NM_020408.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.02

Variant links:

Genes affected

LYRM4 (HGNC:21365): (LYR motif containing 4) The protein encoded by this gene is found in both mitochondria and the nucleus, where it binds cysteine desulfurase and helps free inorganic sulfur for Fe/S clusters. Disruption of this gene negatively impacts mitochondrial and cytosolic iron homeostasis. [provided by RefSeq, Sep 2016]

LYRM4 links:

FARS2 (HGNC:21062): (phenylalanyl-tRNA synthetase 2, mitochondrial) This gene encodes a protein that transfers phenylalanine to its cognate tRNA. This protein localizes to the mitochondrion and plays a role in mitochondrial protein translation. Mutations in this gene can cause combined oxidative phosphorylation deficiency 14 (Alpers encephalopathy). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

FARS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-5260579-C-G is Benign according to our data. Variant chr6-5260579-C-G is described in ClinVar as [Benign]. Clinvar id is 1292135.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYRM4	NM_020408.6 link	c.86+69G>C		intron_variant	Intron 1 of 2	ENST00000330636.9	NP_065141.3	Q9HD34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYRM4	ENST00000330636.9 link	c.86+69G>C		intron_variant	Intron 1 of 2	1	NM_020408.6	ENSP00000418787.1		Q9HD34

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

59706

AN:

151892

Hom.:

15339

Cov.:

show subpopulations

Gnomad AFR

AF:

0.736

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.259

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.386

GnomAD4 exome

AF:

0.193

AC:

215146

AN:

1114044

Hom.:

36522

AF XY:

0.194

AC XY:

108219

AN XY:

558474

show subpopulations

Gnomad4 AFR exome

AF:

0.749

Gnomad4 AMR exome

AF:

0.340

Gnomad4 ASJ exome

AF:

0.229

Gnomad4 EAS exome

AF:

0.230

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.194

Gnomad4 NFE exome

AF:

0.171

Gnomad4 OTH exome

AF:

0.232

GnomAD4 genome

AF:

0.393

AC:

59794

AN:

152004

Hom.:

15378

Cov.:

AF XY:

0.385

AC XY:

28644

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.736

Gnomad4 AMR

AF:

0.369

Gnomad4 ASJ

AF:

0.253

Gnomad4 EAS

AF:

0.260

Gnomad4 SAS

AF:

0.172

Gnomad4 FIN

AF:

0.217

Gnomad4 NFE

AF:

0.254

Gnomad4 OTH

AF:

0.382

Alfa

AF:

0.333

Hom.:

1373

Bravo

AF:

0.424

Asia WGS

AF:

0.256

AC:

891

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 06, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 21968932) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.3

DANN

Benign

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over