rs762445305

Variant names:

• chr6-117329360-A-C
• 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. Variant got 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. 15/21 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

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]

ENSG00000282218 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROS1	NM_001378902.1	c.5317T>G	p.Cys1773Gly	missense_variant	Exon 33 of 44	ENST00000368507.8	NP_001365831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROS1	ENST00000368507.8	c.5317T>G	p.Cys1773Gly	missense_variant	Exon 33 of 44	5	NM_001378902.1	ENSP00000357493.3
ROS1	ENST00000368508.7	c.5335T>G	p.Cys1779Gly	missense_variant	Exon 32 of 43	1		ENSP00000357494.3
ENSG00000282218	ENST00000467125.1	c.548-7966T>G		intron_variant	Intron 4 of 6	2		ENSP00000487717.1
ROS1	ENST00000403284.2	c.256T>G	p.Cys86Gly	missense_variant	Exon 2 of 3	2		ENSP00000384647.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.32	N;N;N
REVEL	Benign	0.050
Sift	Benign	0.086	T;T;D
Sift4G	Uncertain	0.051	T;T;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-117650523;