NM_006639.4:c.349A>G

Variant names:

• chrX-78273398-T-C
• NM_006639.4:c.349A>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006639.4(CYSLTR1):​c.349A>G​(p.Met117Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: CYSLTR1 NM_006639.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.96

Genes affected

CYSLTR1 (HGNC:17451): (cysteinyl leukotriene receptor 1) This gene encodes a member of the G-protein coupled receptor 1 family. The encoded protein is a receptor for cysteinyl leukotrienes, and is involved in mediating bronchoconstriction via activation of a phosphatidylinositol-calcium second messenger system. Activation of the encoded receptor results in contraction and proliferation of bronchial smooth muscle cells, eosinophil migration, and damage to the mucus layer in the lung. Upregulation of this gene is associated with asthma and dysregulation may also be implicated in cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYSLTR1	NM_006639.4	c.349A>G	p.Met117Val	missense_variant	Exon 3 of 3	ENST00000373304.4	NP_006630.1
CYSLTR1	NM_001282186.2	c.349A>G	p.Met117Val	missense_variant	Exon 2 of 2		NP_001269115.1
CYSLTR1	NM_001282187.2	c.349A>G	p.Met117Val	missense_variant	Exon 4 of 4		NP_001269116.1
CYSLTR1	NM_001282188.2	c.349A>G	p.Met117Val	missense_variant	Exon 4 of 4		NP_001269117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYSLTR1	ENST00000373304.4	c.349A>G	p.Met117Val	missense_variant	Exon 3 of 3	1	NM_006639.4	ENSP00000362401.3
CYSLTR1	ENST00000614798.1	c.349A>G	p.Met117Val	missense_variant	Exon 2 of 2	1		ENSP00000478492.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.349A>G (p.M117V) alteration is located in exon 3 (coding exon 1) of the CYSLTR1 gene. This alteration results from a A to G substitution at nucleotide position 349, causing the methionine (M) at amino acid position 117 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	0.32
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.81	.;T
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Uncertain	-0.087	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.2	N;.
REVEL	Uncertain	0.50
Sift	Uncertain	0.010	D;.
Sift4G	Benign	0.19	T;T
Polyphen		0.99	D;D
Vest4		0.75
MutPred		0.52		Gain of catalytic residue at M117 (P = 0.0756);Gain of catalytic residue at M117 (P = 0.0756);
MVP		0.98
MPC		0.037
ClinPred		0.92	D
GERP RS		4.5
Varity_R		0.74
gMVP		0.59

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: chrX-77528895;