rs7752203

chr6-5260579-C-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

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/exons	MANE	UniProt
LYRM4	NM_020408.6	c.86+69G>C		intron_variant		ENST00000330636.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYRM4	ENST00000330636.9	c.86+69G>C		intron_variant		1	NM_020408.6	P1

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

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.: 32 AF XY: 0.385 AC XY: 28644 AN XY: 74312

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

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

Other links and lift over

dbSNP: rs7752203; hg19: chr6-5260812;