16-20924012-C-T

Variant names:

• chr16-20924012-C-T
• rs2083340604
• NM_001128302.3:c.265C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001128302.3(LYRM1):​c.265C>T​(p.Pro89Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000484 in 1,446,532 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: LYRM1 NM_001128302.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.09

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYRM1	NM_001128302.3	c.265C>T	p.Pro89Ser	missense_variant	Exon 4 of 4	ENST00000567954.6	NP_001121774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYRM1	ENST00000567954.6	c.265C>T	p.Pro89Ser	missense_variant	Exon 4 of 4	1	NM_001128302.3	ENSP00000457333.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000484 AC: 7 AN: 1446532 Hom.: 0 Cov.: 27 AF XY: 0.00000278 AC XY: 2 AN XY: 720274

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000635

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.265C>T (p.P89S) alteration is located in exon 5 (coding exon 3) of the LYRM1 gene. This alteration results from a C to T substitution at nucleotide position 265, causing the proline (P) at amino acid position 89 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T;T;T;T;T;T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	.;.;.;D;.;.
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.48	T;T;T;T;T;T
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.2	M;M;M;M;M;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.4	D;D;D;D;D;D
REVEL	Uncertain	0.57
Sift	Benign	0.14	T;T;T;T;T;T
Sift4G	Uncertain	0.052	T;T;T;T;T;T
Polyphen		0.98	D;D;D;D;D;D
Vest4		0.64
MutPred		0.30		Loss of catalytic residue at P88 (P = 0.0099);Loss of catalytic residue at P88 (P = 0.0099);Loss of catalytic residue at P88 (P = 0.0099);Loss of catalytic residue at P88 (P = 0.0099);Loss of catalytic residue at P88 (P = 0.0099);Loss of catalytic residue at P88 (P = 0.0099);
MVP		0.18
MPC		0.33
ClinPred		0.96	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.70

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: rs2083340604; hg19: chr16-20935334;