rs375253180

Variant names:

• chr16-20924081-C-A
• rs375253180
• NM_001128302.3:c.334C>A

Variant summary

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

The NM_001128302.3(LYRM1):​c.334C>A​(p.Pro112Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,611,360 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: LYRM1 NM_001128302.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.09
• 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: NM_001128302.3. 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.334C>A	p.Pro112Thr	missense	Exon 4 of 4	NP_001121774.1	O43325
	LYRM1	NM_001369631.1		c.349C>A	p.Pro117Thr	missense	Exon 6 of 6	NP_001356560.1
	LYRM1	NM_001128301.3		c.334C>A	p.Pro112Thr	missense	Exon 5 of 5	NP_001121773.1	O43325

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYRM1	ENST00000567954.6	TSL:1 MANE Select	c.334C>A	p.Pro112Thr	missense	Exon 4 of 4	ENSP00000457333.1	O43325
	LYRM1	ENST00000396052.3	TSL:1	c.334C>A	p.Pro112Thr	missense	Exon 6 of 6	ENSP00000379367.2	O43325
	LYRM1	ENST00000412082.6	TSL:1	c.67C>A	p.Pro23Thr	missense	Exon 3 of 3	ENSP00000396868.2	H3BNA8

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000160 AC: 4 AN: 250096 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1459168 Hom.: 0 Cov.: 28 AF XY: 0.0000138 AC XY: 10 AN XY: 726120

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1109848

Other (OTH) AF: 0.0000166 AC: 1 AN: 60298

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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: 2090

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000189

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

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	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.40
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		6.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.49
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.61	P
Vest4		0.91
MVP		0.20
MPC		0.34
ClinPred		0.92	D
GERP RS		3.9
Varity_R		0.79
gMVP		0.70
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs375253180; hg19: chr16-20935403;