17-17495298-T-C

Variant names:

• chr17-17495298-T-C
• rs1024822023
• NM_016084.5:c.673A>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.673A>G​(p.Lys225Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: RASD1 NM_016084.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.27
• 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=0.27362487).

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.673A>G	p.Lys225Glu	missense	Exon 2 of 2	NP_057168.1	Q9Y272-1
	RASD1	NM_001199989.2		c.*230A>G		3_prime_UTR	Exon 2 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.673A>G	p.Lys225Glu	missense	Exon 2 of 2	ENSP00000225688.3	Q9Y272-1
	RASD1	ENST00000962192.1		c.670A>G	p.Lys224Glu	missense	Exon 2 of 2	ENSP00000632251.1
	RASD1	ENST00000579152.1	TSL:2	c.*230A>G		3_prime_UTR	Exon 2 of 2	ENSP00000463388.1	Q9Y272-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152210 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152210 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74354

African (AFR) AF: 0.0000241 AC: 1 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

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	Uncertain	0.45
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.057
Eigen_PC	Benign	0.020
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.3
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.38
Sift	Benign	0.28	T
Sift4G	Benign	0.79	T
Polyphen		0.23	B
Vest4		0.43
MutPred		0.40		Loss of helix (P = 3e-04)
MVP		0.91
MPC		1.0
ClinPred		0.86	D
GERP RS		4.2
Varity_R		0.21
gMVP		0.61

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

dbSNP: rs1024822023; hg19: chr17-17398612;