6-5186705-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_020408.6(LYRM4):c.207+29913G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000387 in 988,570 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: LYRM4 NM_020408.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.319

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 6-5186705-C-T is Benign according to our data. Variant chr6-5186705-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1316427.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYRM4	NM_020408.6	c.207+29913G>A		intron_variant		ENST00000330636.9
LYRM4-AS1	NR_126015.1	n.374-51003C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYRM4	ENST00000330636.9	c.207+29913G>A		intron_variant		1	NM_020408.6	P1

Frequencies

GnomAD3 genomes AF: 0.00166 AC: 253 AN: 152094 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.000155 AC: 130 AN: 836358 Hom.: 0 Cov.: 21 AF XY: 0.000158 AC XY: 61 AN XY: 387278

Gnomad4 AFR exome AF: 0.000191

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000112

Gnomad4 FIN exome AF: 0.00839

Gnomad4 NFE exome AF: 0.000144

Gnomad4 OTH exome AF: 0.000255

GnomAD4 genome AF: 0.00166 AC: 253 AN: 152212 Hom.: 2 Cov.: 32 AF XY: 0.00236 AC XY: 176 AN XY: 74422

Gnomad4 AFR AF: 0.000458

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.0180

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000847 Hom.: 0

Bravo AF: 0.000431

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.64
Dann	Benign	0.13

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: rs182220319; hg19: chr6-5186939;