17-27882675-G-A

Variant names:

• chr17-27882675-G-A
• NM_001076680.3:c.20C>T

Variant summary

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

The NM_001076680.3(LYRM9):​c.20C>T​(p.Ala7Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,451,870 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. A7T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LYRM9 NM_001076680.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.72
• 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=0.36471665).

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.20C>T	p.Ala7Val	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.20C>T	p.Ala7Val	missense	Exon 2 of 4	ENSP00000368396.3	A8MSI8
	ENSG00000266202	ENST00000582441.1	TSL:4	c.20C>T	p.Ala7Val	missense	Exon 2 of 5	ENSP00000462879.1	J3KTA2
	LYRM9	ENST00000508862.5	TSL:3	c.20C>T	p.Ala7Val	missense	Exon 2 of 5	ENSP00000426554.1	D6RFL2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451870 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 721116

African (AFR) AF: 0.00 AC: 0 AN: 33270

American (AMR) AF: 0.00 AC: 0 AN: 43524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25896

East Asian (EAS) AF: 0.00 AC: 0 AN: 39276

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52612

Middle Eastern (MID) AF: 0.000179 AC: 1 AN: 5596

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107504

Other (OTH) AF: 0.00 AC: 0 AN: 60032

GnomAD4 genome Cov.: 32

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	0.19
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.36	T
MetaSVM	Uncertain	-0.26	T
PhyloP100		6.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.21
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.020	D
Polyphen		0.99	D
Vest4		0.64
MVP		0.23
MPC		0.13
ClinPred		0.83	D
GERP RS		5.3
Varity_R		0.13
gMVP		0.46

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

hg19: chr17-26209701;