chr6-5109748-T-TC

Position:

• chr6-5109748-T-TC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020408.6(LYRM4):​c.208-258dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,152 control chromosomes in the GnomAD database, including 2,681 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2681 hom., cov: 29)
• Consequence: LYRM4 NM_020408.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.72

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 6-5109748-T-TC is Benign according to our data. Variant chr6-5109748-T-TC is described in ClinVar as [Benign]. Clinvar id is 680636.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYRM4	NM_020408.6	c.208-258dupG		intron_variant		ENST00000330636.9	NP_065141.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYRM4	ENST00000330636.9	c.208-258_208-257insG		intron_variant		1	NM_020408.6	ENSP00000418787.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27404 AN: 152034 Hom.: 2679 Cov.: 29

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0925

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.180 AC: 27428 AN: 152152 Hom.: 2681 Cov.: 29 AF XY: 0.176 AC XY: 13096 AN XY: 74378

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.0934

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.154

Alfa AF: 0.0577 Hom.: 80

Bravo AF: 0.186

Asia WGS AF: 0.0620 AC: 215 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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs56841759; hg19: chr6-5109982;