rs7752203

Variant names:

• chr6-5260579-C-G
• rs7752203
• NM_020408.6:c.86+69G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-5260579-C-G
• chr6-5260579-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02
• Publications: 9 publications found

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]

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 Gene-Disease associations (from GenCC):

• metabolic disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• combined oxidative phosphorylation defect type 14

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary spastic paraplegia 77

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.86+69G>C		intron_variant	Intron 1 of 2	ENST00000330636.9	NP_065141.3

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59706 AN: 151892 Hom.: 15339 Cov.: 32

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

African (AFR) AF: 0.749 AC: 16211 AN: 21644

American (AMR) AF: 0.340 AC: 11020 AN: 32438

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 5148 AN: 22518

East Asian (EAS) AF: 0.230 AC: 7569 AN: 32884

South Asian (SAS) AF: 0.158 AC: 11887 AN: 75082

European-Finnish (FIN) AF: 0.194 AC: 6153 AN: 31718

Middle Eastern (MID) AF: 0.270 AC: 913 AN: 3376

European-Non Finnish (NFE) AF: 0.171 AC: 145234 AN: 846904

Other (OTH) AF: 0.232 AC: 11011 AN: 47480

GnomAD4 genome AF: 0.393 AC: 59794 AN: 152004 Hom.: 15378 Cov.: 32 AF XY: 0.385 AC XY: 28644 AN XY: 74312

African (AFR) AF: 0.736 AC: 30485 AN: 41424

American (AMR) AF: 0.369 AC: 5632 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 879 AN: 3468

East Asian (EAS) AF: 0.260 AC: 1330 AN: 5124

South Asian (SAS) AF: 0.172 AC: 828 AN: 4824

European-Finnish (FIN) AF: 0.217 AC: 2295 AN: 10578

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17287 AN: 67990

Other (OTH) AF: 0.382 AC: 807 AN: 2110

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

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
PhyloP100		-1.0
PromoterAI		0.089	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7752203; hg19: chr6-5260812;