6-117321332-C-G

Variant names:

• chr6-117321332-C-G
• NM_001378902.1:c.5686G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378902.1(ROS1):​c.5686G>C​(p.Glu1896Gln) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ROS1 NM_001378902.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.37

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=0.24610418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROS1	NM_001378902.1	c.5686G>C	p.Glu1896Gln	missense_variant	Exon 36 of 44	ENST00000368507.8	NP_001365831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROS1	ENST00000368507.8	c.5686G>C	p.Glu1896Gln	missense_variant	Exon 36 of 44	5	NM_001378902.1	ENSP00000357493.3
ROS1	ENST00000368508.7	c.5704G>C	p.Glu1902Gln	missense_variant	Exon 35 of 43	1		ENSP00000357494.3
ENSG00000282218	ENST00000467125.1	c.610G>C	p.Glu204Gln	missense_variant	Exon 5 of 7	2		ENSP00000487717.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.090	T;.;.
Eigen	Benign	0.075
Eigen_PC	Benign	0.097
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.0	M;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.54	N;N;.
REVEL	Benign	0.11
Sift	Benign	0.20	T;T;.
Sift4G	Uncertain	0.042	D;D;D
Polyphen		0.95	P;.;.
Vest4		0.11
MutPred		0.33		Loss of stability (P = 0.0644);.;.;
MVP		0.50
MPC		0.16
ClinPred		0.76	D
GERP RS		4.3
Varity_R		0.061
gMVP		0.48

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: chr6-117642495;