NM_001076680.3:c.46C>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

Genes affected

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

ENSG00000266202 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001076680.3. 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
	LYRM9	NM_001076680.3	MANE Select	c.46C>T	p.Leu16Phe	missense	Exon 2 of 4	NP_001070148.1	A8MSI8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYRM9	ENST00000379102.8	TSL:2 MANE Select	c.46C>T	p.Leu16Phe	missense	Exon 2 of 4	ENSP00000368396.3	A8MSI8
	ENSG00000266202	ENST00000582441.1	TSL:4	c.46C>T	p.Leu16Phe	missense	Exon 2 of 5	ENSP00000462879.1	J3KTA2
	LYRM9	ENST00000508862.5	TSL:3	c.46C>T	p.Leu16Phe	missense	Exon 2 of 5	ENSP00000426554.1	D6RFL2

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

African (AFR) AF: 0.00 AC: 0 AN: 33266

American (AMR) AF: 0.00 AC: 0 AN: 43434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25932

East Asian (EAS) AF: 0.00 AC: 0 AN: 39206

South Asian (SAS) AF: 0.00 AC: 0 AN: 83920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5442

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1107358

Other (OTH) AF: 0.0000167 AC: 1 AN: 59964

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000330 Hom.: 0

Bravo AF: 0.0000302

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	0.77
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	0.51	D
PhyloP100		3.6
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-4.0	D
REVEL	Pathogenic	0.72
Sift	Benign	0.059	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	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
Mutation Taster		=51/49	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: rs1403182753; hg19: chr17-26209675;