rs762445305

Variant names:

• chr6-117329360-A-C
• rs762445305
• NM_001378902.1:c.5317T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-117329360-A-C
• chr6-117329360-A-G
• chr6-117329360-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378902.1(ROS1):​c.5317T>G​(p.Cys1773Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C1773R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ROS1 NM_001378902.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 0 publications found

Genes affected

ROS1 (HGNC:10261): (ROS proto-oncogene 1, receptor tyrosine kinase) This proto-oncogene, highly-expressed in a variety of tumor cell lines, belongs to the sevenless subfamily of tyrosine kinase insulin receptor genes. The protein encoded by this gene is a type I integral membrane protein with tyrosine kinase activity. The protein may function as a growth or differentiation factor receptor. [provided by RefSeq, Jul 2008]

ROS1 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center
• breast cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000282218 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17848384).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378902.1. 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
	ROS1	NM_001378902.1	MANE Select	c.5317T>G	p.Cys1773Gly	missense	Exon 33 of 44	NP_001365831.1	Q5H8Y1
	ROS1	NM_002944.3		c.5335T>G	p.Cys1779Gly	missense	Exon 32 of 43	NP_002935.2
	ROS1	NM_001378891.1		c.5323T>G	p.Cys1775Gly	missense	Exon 33 of 44	NP_001365820.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROS1	ENST00000368507.8	TSL:5 MANE Select	c.5317T>G	p.Cys1773Gly	missense	Exon 33 of 44	ENSP00000357493.3	Q5H8Y1
	ROS1	ENST00000368508.7	TSL:1	c.5335T>G	p.Cys1779Gly	missense	Exon 32 of 43	ENSP00000357494.3	P08922
	ENSG00000282218	ENST00000467125.1	TSL:2	c.548-7966T>G		intron	N/A	ENSP00000487717.1	A0A0J9YVX5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.8
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.050
Sift	Benign	0.086	T
Sift4G	Uncertain	0.051	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.77		Gain of disorder (P = 0.0277)
MVP		0.16
MPC		0.028
ClinPred		0.15	T
GERP RS		3.5
Varity_R		0.11
gMVP		0.48
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs762445305; hg19: chr6-117650523;