17-27882675-G-A

Position:

• chr17-27882675-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

Genes affected

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

ENSG00000266202 (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=0.36471665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYRM9	NM_001076680.3	c.20C>T	p.Ala7Val	missense_variant	2/4	ENST00000379102.8	NP_001070148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYRM9	ENST00000379102.8	c.20C>T	p.Ala7Val	missense_variant	2/4	2	NM_001076680.3	ENSP00000368396.3
ENSG00000266202	ENST00000582441.1	c.20C>T	p.Ala7Val	missense_variant	2/5	4		ENSP00000462879.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jul 09, 2024

The c.20C>T (p.A7V) alteration is located in exon 2 (coding exon 1) of the LYRM9 gene. This alteration results from a C to T substitution at nucleotide position 20, causing the alanine (A) at amino acid position 7 to be replaced by a valine (V). 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	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;.;.;T;.;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D;.;.;D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.36	T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.26	T
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.7	.;.;.;N;N;.;.
REVEL	Benign	0.21
Sift	Uncertain	0.0090	.;.;.;D;D;.;.
Sift4G	Uncertain	0.020	D;D;D;D;D;D;.
Polyphen		0.99	.;D;.;.;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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-26209701;