dbSNP rs774190385: RASD1:p.Ala247Ser (chr17-17495232-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016084.5(RASD1):c.739G>T(p.Ala247Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,454,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. A247T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RASD1
NM_016084.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.90

Publications

0 publications found

Variant links:

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]

RASD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.23097545).

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.739G>T	p.Ala247Ser	missense	Exon 2 of 2	NP_057168.1	Q9Y272-1
	RASD1	NM_001199989.2		c.*296G>T		3_prime_UTR	Exon 2 of 2	NP_001186918.1	Q9Y272-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RASD1	ENST00000225688.4	TSL:1 MANE Select	c.739G>T	p.Ala247Ser	missense	Exon 2 of 2	ENSP00000225688.3	Q9Y272-1
RASD1	ENST00000962192.1		c.736G>T	p.Ala246Ser	missense	Exon 2 of 2	ENSP00000632251.1
RASD1	ENST00000579152.1	TSL:2	c.*296G>T		3_prime_UTR	Exon 2 of 2	ENSP00000463388.1	Q9Y272-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000447

AC:

AN:

223594

AF XY:

0.00000807

show subpopulations

Gnomad AFR exome

AF:

0.0000768

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454888

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723540

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33352

American (AMR)

AF:

0.00

AC:

AN:

43992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26014

East Asian (EAS)

AF:

0.00

AC:

AN:

39456

South Asian (SAS)

AF:

0.00

AC:

AN:

85734

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50856

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5480

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109988

Other (OTH)

AF:

0.00

AC:

AN:

60016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.29

Eigen

Benign

-0.059

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.80

M_CAP

Benign

0.047

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.6

PhyloP100

3.9

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.17

REVEL

Benign

0.13

Sift

Benign

0.58

Sift4G

Benign

0.84

Polyphen

0.021

Vest4

0.34

MutPred

0.23

Gain of disorder (P = 0.0401)

MVP

0.81

MPC

0.66

ClinPred

0.19

GERP RS

5.3

Varity_R

0.12

gMVP

0.45

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over