chr17-27882676-C-T

Variant names:

• chr17-27882676-C-T
• rs758227049
• NM_001076680.3:c.19G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001076680.3(LYRM9):​c.19G>A​(p.Ala7Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000344 in 1,452,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A7V) has been classified 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: 5.16
• Publications: 0 publications found

Genes affected

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

ENSG00000266202 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28849065).

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.19G>A	p.Ala7Thr	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.19G>A	p.Ala7Thr	missense	Exon 2 of 4	ENSP00000368396.3	A8MSI8
	ENSG00000266202	ENST00000582441.1	TSL:4	c.19G>A	p.Ala7Thr	missense	Exon 2 of 5	ENSP00000462879.1	J3KTA2
	LYRM9	ENST00000508862.5	TSL:3	c.19G>A	p.Ala7Thr	missense	Exon 2 of 5	ENSP00000426554.1	D6RFL2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000215 AC: 5 AN: 232890 AF XY: 0.0000238

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1452036 Hom.: 0 Cov.: 30 AF XY: 0.00000416 AC XY: 3 AN XY: 721212

African (AFR) AF: 0.00 AC: 0 AN: 33284

American (AMR) AF: 0.00 AC: 0 AN: 43528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25890

East Asian (EAS) AF: 0.00 AC: 0 AN: 39286

South Asian (SAS) AF: 0.0000594 AC: 5 AN: 84184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52652

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5600

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107572

Other (OTH) AF: 0.00 AC: 0 AN: 60040

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000248 AC: 3

Asia WGS AF: 0.000577 AC: 4 AN: 3478

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	0.18
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.018	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	-0.20	T
PhyloP100		5.2
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.20
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.021	D
Polyphen		0.97	D
Vest4		0.31
MVP		0.29
MPC		0.13
ClinPred		0.44	T
GERP RS		5.3
Varity_R		0.11
gMVP		0.45
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs758227049; hg19: chr17-26209702;