17-27882649-G-A

Variant names:

• chr17-27882649-G-A
• rs1403182753
• NM_001076680.3:c.46C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001076680.3(LYRM9):​c.46C>T​(p.Leu16Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000345 in 1,450,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: LYRM9 NM_001076680.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60

Genes affected

LYRM9 (HGNC:27314): (LYR motif containing 9)

ENSG00000266202 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.823

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYRM9	NM_001076680.3	c.46C>T	p.Leu16Phe	missense_variant	Exon 2 of 4	ENST00000379102.8	NP_001070148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYRM9	ENST00000379102.8	c.46C>T	p.Leu16Phe	missense_variant	Exon 2 of 4	2	NM_001076680.3	ENSP00000368396.3
ENSG00000266202	ENST00000582441.1	c.46C>T	p.Leu16Phe	missense_variant	Exon 2 of 5	4		ENSP00000462879.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1450900 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 720614

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: 0.00000361

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000330 Hom.: 0

Bravo AF: 0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.46C>T (p.L16F) alteration is located in exon 2 (coding exon 1) of the LYRM9 gene. This alteration results from a C to T substitution at nucleotide position 46, causing the leucine (L) at amino acid position 16 to be replaced by a phenylalanine (F). 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	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	.;T;.;.;T;.;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D;.;.;D;D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.82	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.51	D
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-4.0	.;D;.;D;D;.;.
REVEL	Pathogenic	0.72
Sift	Benign	0.059	.;.;.;T;T;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;.
Polyphen		1.0	.;D;.;.;D;.;.
Vest4		0.73
MVP		0.95
MPC		0.14
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.23
gMVP		0.65

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: rs1403182753; hg19: chr17-26209675;