Genetic Variant NM_020408.6:c.207+29952C>A (chr6-5186666-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_020408.6(LYRM4):c.207+29952C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 981,958 control chromosomes in the GnomAD database, including 32,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.29 ( 6820 hom., cov: 32)

Exomes 𝑓: 0.25 ( 25981 hom. )

Consequence

LYRM4
NM_020408.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.26

Variant links:

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 links:

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

LYRM4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 6-5186666-G-T is Benign according to our data. Variant chr6-5186666-G-T is described in ClinVar as [Benign]. Clinvar id is 1283276.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYRM4	NM_020408.6 link	c.207+29952C>A		intron_variant	Intron 2 of 2	ENST00000330636.9	NP_065141.3	Q9HD34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYRM4	ENST00000330636.9 link	c.207+29952C>A		intron_variant	Intron 2 of 2	1	NM_020408.6	ENSP00000418787.1		Q9HD34

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44470

AN:

151952

Hom.:

6815

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.268

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.250

Gnomad OTH

AF:

0.297

GnomAD4 exome

AF:

0.247

AC:

205334

AN:

829888

Hom.:

25981

Cov.:

AF XY:

0.247

AC XY:

94688

AN XY:

383506

show subpopulations

Gnomad4 AFR exome

AF:

0.407

Gnomad4 AMR exome

AF:

0.290

Gnomad4 ASJ exome

AF:

0.255

Gnomad4 EAS exome

AF:

0.254

Gnomad4 SAS exome

AF:

0.195

Gnomad4 FIN exome

AF:

0.295

Gnomad4 NFE exome

AF:

0.245

Gnomad4 OTH exome

AF:

0.243

GnomAD4 genome

AF:

0.293

AC:

44495

AN:

152070

Hom.:

6820

Cov.:

AF XY:

0.290

AC XY:

21575

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.390

Gnomad4 AMR

AF:

0.299

Gnomad4 ASJ

AF:

0.268

Gnomad4 EAS

AF:

0.242

Gnomad4 SAS

AF:

0.194

Gnomad4 FIN

AF:

0.270

Gnomad4 NFE

AF:

0.250

Gnomad4 OTH

AF:

0.294

Alfa

AF:

0.145

Hom.:

274

Bravo

AF:

0.302

Asia WGS

AF:

0.236

AC:

821

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.21

DANN

Benign

0.26

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over