17-17495985-G-C

Variant names:

• chr17-17495985-G-C
• NM_016084.5:c.197C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016084.5(RASD1):​c.197C>G​(p.Ser66Cys) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S66P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RASD1 NM_016084.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.49
• Publications: 0 publications found

Genes affected

RASD1 (HGNC:15828): (ras related dexamethasone induced 1) This gene encodes a member of the Ras superfamily of small GTPases and is induced by dexamethasone. The encoded protein is an activator of G-protein signaling and acts as a direct nucleotide exchange factor for Gi-Go proteins. This protein interacts with the neuronal nitric oxide adaptor protein CAPON, and a nuclear adaptor protein FE65, which interacts with the Alzheimer's disease amyloid precursor protein. This gene may play a role in dexamethasone-induced alterations in cell morphology, growth and cell-extracellular matrix interactions. Epigenetic inactivation of this gene is closely correlated with resistance to dexamethasone in multiple myeloma cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34277546).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016084.5. 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
	RASD1	NM_016084.5	MANE Select	c.197C>G	p.Ser66Cys	missense	Exon 1 of 2	NP_057168.1	Q9Y272-1
	RASD1	NM_001199989.2		c.197C>G	p.Ser66Cys	missense	Exon 1 of 2	NP_001186918.1	Q9Y272-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASD1	ENST00000225688.4	TSL:1 MANE Select	c.197C>G	p.Ser66Cys	missense	Exon 1 of 2	ENSP00000225688.3	Q9Y272-1
	RASD1	ENST00000962192.1		c.197C>G	p.Ser66Cys	missense	Exon 1 of 2	ENSP00000632251.1
	RASD1	ENST00000579152.1	TSL:2	c.197C>G	p.Ser66Cys	missense	Exon 1 of 2	ENSP00000463388.1	Q9Y272-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	0.0045	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	23
DANN	Benign	0.89
DEOGEN2	Pathogenic	0.84	D
Eigen	Benign	-0.10
Eigen_PC	Benign	0.019
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.5
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.33
Sift	Benign	0.086	T
Sift4G	Benign	0.073	T
Polyphen		0.0010	B
Vest4		0.21
MutPred		0.50		Loss of ubiquitination at K63 (P = 0.1403)
MVP		0.87
MPC		0.69
ClinPred		0.75	D
GERP RS		3.8
PromoterAI		-0.032	Neutral
Varity_R		0.40
gMVP		0.46

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

Other links and lift over

hg19: chr17-17399299;