17-27880319-C-A

Variant names:

• chr17-27880319-C-A
• rs1403244941
• NM_001076680.3:c.174G>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.174G>T​(p.Gln58His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,062 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 (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: LYRM9 NM_001076680.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.67
• Publications: 1 publications found

Genes affected

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

ENSG00000266202 (HGNC:):

LYRM9-AS1 (HGNC:58314):

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=0.26443875).

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.174G>T	p.Gln58His	missense	Exon 3 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.174G>T	p.Gln58His	missense	Exon 3 of 4	ENSP00000368396.3	A8MSI8
	ENSG00000266202	ENST00000582441.1	TSL:4	c.174G>T	p.Gln58His	missense	Exon 3 of 5	ENSP00000462879.1	J3KTA2
	LYRM9	ENST00000508862.5	TSL:3	c.174G>T	p.Gln58His	missense	Exon 3 of 5	ENSP00000426554.1	D6RFL2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1458062 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 724824

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000598 AC: 2 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 85266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110106

Other (OTH) AF: 0.0000332 AC: 2 AN: 60274

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000266003), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

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	Uncertain	0.56
BayesDel_addAF	Benign	-0.0055	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	23
DANN	Benign	0.81
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.024
Eigen_PC	Benign	0.015
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.54	T
PhyloP100		1.7
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.94	P
Vest4		0.22
MVP		0.75
MPC		0.13
ClinPred		0.88	D
GERP RS		3.3
Varity_R		0.32
gMVP		0.44
Mutation Taster		=78/22	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: rs1403244941; hg19: chr17-26207345;