17-27880319-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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

Genes affected

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

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26443875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYRM9	NM_001076680.3	c.174G>T	p.Gln58His	missense_variant	3/4	ENST00000379102.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYRM9	ENST00000379102.8	c.174G>T	p.Gln58His	missense_variant	3/4	2	NM_001076680.3	P1
	ENST00000581901.1	n.1348C>A		non_coding_transcript_exon_variant	2/2	2

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

Gnomad4 AFR exome AF: 0.0000598

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: 0.00

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.174G>T (p.Q58H) alteration is located in exon 3 (coding exon 2) of the LYRM9 gene. This alteration results from a G to T substitution at nucleotide position 174, causing the glutamine (Q) at amino acid position 58 to be replaced by a histidine (H). 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	Uncertain	0.56
BayesDel_addAF	Benign	-0.0055	T
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	23
Dann	Benign	0.81
Eigen	Benign	0.024
Eigen_PC	Benign	0.015
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.80	T;.;.;T;T;T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.26	T;T;T;T;T;T
MetaSVM	Benign	-0.54	T
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Uncertain	0.55	T
Sift4G	Uncertain	0.0080	D;D;D;D;D;D
Polyphen		0.94	.;P;.;.;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

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: rs1403244941; hg19: chr17-26207345;