rs1301142742

Positions:

• chr6-5260727-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020408.6(LYRM4):​c.7G>A​(p.Ala3Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000215 in 1,397,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LYRM4 NM_020408.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25773942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYRM4	NM_020408.6	c.7G>A	p.Ala3Thr	missense_variant	1/3	ENST00000330636.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYRM4	ENST00000330636.9	c.7G>A	p.Ala3Thr	missense_variant	1/3	1	NM_020408.6	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1397398 Hom.: 0 Cov.: 37 AF XY: 0.00000145 AC XY: 1 AN XY: 689702

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Combined oxidative phosphorylation deficiency 19 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Dec 09, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;.;T;T;T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.12	N
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.26	T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationTaster	Benign	0.80	D;D;D;D;N
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.4	N;D;N;N;N
REVEL	Benign	0.067
Sift	Uncertain	0.010	D;D;T;D;D
Sift4G	Uncertain	0.042	D;D;D;D;D
Polyphen		0.34	B;.;D;.;.
Vest4		0.39
MutPred		0.18		Gain of phosphorylation at A3 (P = 0.06);Gain of phosphorylation at A3 (P = 0.06);Gain of phosphorylation at A3 (P = 0.06);Gain of phosphorylation at A3 (P = 0.06);Gain of phosphorylation at A3 (P = 0.06);
MVP		0.65
MPC		0.34
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.54
gMVP		0.064

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: rs1301142742; hg19: chr6-5260960;