6-5143958-C-T

Position:

• chr6-5143958-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_020408.6(LYRM4):​c.208-34467G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,108 control chromosomes in the GnomAD database, including 49,046 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.80 (49046 hom., cov: 33)
• Consequence: LYRM4 NM_020408.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.01

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 6-5143958-C-T is Benign according to our data. Variant chr6-5143958-C-T is described in ClinVar as [Benign]. Clinvar id is 680627.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYRM4	NM_020408.6	c.208-34467G>A		intron_variant		ENST00000330636.9
LYRM4-AS1	NR_126015.1	n.373+71224C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYRM4	ENST00000330636.9	c.208-34467G>A		intron_variant		1	NM_020408.6	P1

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121817 AN: 151990 Hom.: 49001 Cov.: 33

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.770

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

GnomAD4 genome AF: 0.802 AC: 121917 AN: 152108 Hom.: 49046 Cov.: 33 AF XY: 0.804 AC XY: 59791 AN XY: 74336

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.923

Gnomad4 SAS AF: 0.872

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.772

Alfa AF: 0.796 Hom.: 96890

Bravo AF: 0.792

Asia WGS AF: 0.892 AC: 3099 AN: 3478

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

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Benign	0.79

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: rs399120; hg19: chr6-5144192;