ENST00000412082.6:c.-104C>T

Variant names:

• chr16-20920126-C-T
• rs759338347
• ENST00000412082.6:c.-104C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000412082.6(LYRM1):​c.-104C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000423 in 1,608,118 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: LYRM1 ENST00000412082.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19
• Publications: 0 publications found

Genes affected

LYRM1 (HGNC:25074): (LYR motif containing 1) The protein encoded by this gene belongs to the mitochondrial leucine/tyrosine/arginine motif family of proteins. Proteins of this family are short polypeptides that contain a leucine/tyrosine/arginine motif near the N-terminus. This gene is widely expressed with high levels in omental adipose tissue of obese individuals. In adipose tissue, the protein is localized to the nucleus where it promotes preadipocyte proliferation and lowers the rate of apoptosis to regulate adipose tissue homeostasis. Overexpression of this gene in adipocytes causes abnormal mitochondrial morphology and mitochondrial dysfunction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000412082.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYRM1	NM_001128302.3	MANE Select	c.164C>T	p.Thr55Met	missense	Exon 3 of 4	NP_001121774.1	O43325
	LYRM1	NM_001369631.1		c.179C>T	p.Thr60Met	missense	Exon 5 of 6	NP_001356560.1
	LYRM1	NM_001128301.3		c.164C>T	p.Thr55Met	missense	Exon 4 of 5	NP_001121773.1	O43325

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYRM1	ENST00000412082.6	TSL:1	c.-104C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	ENSP00000396868.2	H3BNA8
	LYRM1	ENST00000562740.5	TSL:1	c.-104C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 4	ENSP00000454759.1	H3BNA8
	LYRM1	ENST00000567954.6	TSL:1 MANE Select	c.164C>T	p.Thr55Met	missense	Exon 3 of 4	ENSP00000457333.1	O43325

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152116 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000320 AC: 8 AN: 250078 AF XY: 0.0000370

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000927

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000412 AC: 60 AN: 1456002 Hom.: 0 Cov.: 29 AF XY: 0.0000359 AC XY: 26 AN XY: 724624

African (AFR) AF: 0.0000900 AC: 3 AN: 33322

American (AMR) AF: 0.0000225 AC: 1 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85978

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000388 AC: 43 AN: 1107196

Other (OTH) AF: 0.000150 AC: 9 AN: 60162

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152116 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74280

African (AFR) AF: 0.0000724 AC: 3 AN: 41420

American (AMR) AF: 0.000197 AC: 3 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.0000547

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.090
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		2.2
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.055	T
Polyphen		0.91	P
Vest4		0.41
MutPred		0.49		Loss of relative solvent accessibility (P = 0.0676)
MVP		0.79
MPC		0.064
ClinPred		0.79	D
GERP RS		5.8
Varity_R		0.25
gMVP		0.64
Mutation Taster		=43/57	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs759338347; hg19: chr16-20931448; COSMIC: COSV54644043;