17-27882676-C-T

Position:

• chr17-27882676-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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 (★).

• 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

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=0.28849065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYRM9	NM_001076680.3	c.19G>A	p.Ala7Thr	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.19G>A	p.Ala7Thr	missense_variant	2/4	2	NM_001076680.3	ENSP00000368396.3
ENSG00000266202	ENST00000582441.1	c.19G>A	p.Ala7Thr	missense_variant	2/5	4		ENSP00000462879.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000215 AC: 5 AN: 232890 Hom.: 0 AF XY: 0.0000238 AC XY: 3 AN XY: 126048

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 SAS exome AF: 0.000178

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

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: 0.0000594

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000248 AC: 3

Asia WGS AF: 0.000577 AC: 4 AN: 3478

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

Jun 06, 2023

The c.19G>A (p.A7T) alteration is located in exon 2 (coding exon 1) of the LYRM9 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the alanine (A) at amino acid position 7 to be replaced by a threonine (T). 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	0.18
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.018	.;T;.;.;T;.;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D;.;.;D;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.29	T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.20	T
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.95	.;.;.;N;N;.;.
REVEL	Benign	0.20
Sift	Uncertain	0.014	.;.;.;D;D;.;.
Sift4G	Uncertain	0.021	D;T;D;D;T;D;.
Polyphen		0.97	.;D;.;.;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs758227049; hg19: chr17-26209702;