rs12529198

Variant names:

• chr6-5151013-A-G
• rs12529198
• NM_020408.6:c.208-41522T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020408.6(LYRM4):​c.208-41522T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,030 control chromosomes in the GnomAD database, including 963 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (963 hom., cov: 32)
• Consequence: LYRM4 NM_020408.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608
• Publications: 12 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]

LYRM4-AS1 (HGNC:52055): (LYRM4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYRM4	NM_020408.6	c.208-41522T>C		intron_variant	Intron 2 of 2	ENST00000330636.9	NP_065141.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYRM4	ENST00000330636.9	c.208-41522T>C		intron_variant	Intron 2 of 2	1	NM_020408.6	ENSP00000418787.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15375 AN: 151918 Hom.: 960 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.0381

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0670

Gnomad OTH AF: 0.0985

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

GnomAD4 genome AF: 0.101 AC: 15381 AN: 152030 Hom.: 963 Cov.: 32 AF XY: 0.104 AC XY: 7732 AN XY: 74312

African (AFR) AF: 0.143 AC: 5940 AN: 41438

American (AMR) AF: 0.124 AC: 1899 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3468

East Asian (EAS) AF: 0.147 AC: 758 AN: 5168

South Asian (SAS) AF: 0.236 AC: 1134 AN: 4808

European-Finnish (FIN) AF: 0.0381 AC: 403 AN: 10564

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0670 AC: 4553 AN: 68000

Other (OTH) AF: 0.0989 AC: 209 AN: 2114

Alfa AF: 0.0833 Hom.: 542

Bravo AF: 0.106

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.90
DANN	Benign	0.46
PhyloP100		-0.61
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: rs12529198; hg19: chr6-5151247;