1-206507742-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000579436.7(RASSF5):​c.140C>T​(p.Pro47Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000816 in 1,471,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

RASSF5
ENST00000579436.7 missense

Scores

1
1
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42
Variant links:
Genes affected
RASSF5 (HGNC:17609): (Ras association domain family member 5) This gene is a member of the Ras association domain family. It functions as a tumor suppressor, and is inactivated in a variety of cancers. The encoded protein localizes to centrosomes and microtubules, and associates with the GTP-activated forms of Ras, Rap1, and several other Ras-like small GTPases. The protein regulates lymphocyte adhesion and suppresses cell growth in response to activated Rap1 or Ras. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.10934746).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RASSF5NM_182663.4 linkuse as main transcriptc.140C>T p.Pro47Leu missense_variant 1/6 ENST00000579436.7 NP_872604.1 Q8WWW0-1A8K5F3
RASSF5NM_182664.4 linkuse as main transcriptc.140C>T p.Pro47Leu missense_variant 1/5 NP_872605.1 Q8WWW0-3A8K5F3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RASSF5ENST00000579436.7 linkuse as main transcriptc.140C>T p.Pro47Leu missense_variant 1/61 NM_182663.4 ENSP00000462099.1 Q8WWW0-1
RASSF5ENST00000581503.6 linkuse as main transcriptc.140C>T p.Pro47Leu missense_variant 1/41 ENSP00000464039.2 A0A075B763
RASSF5ENST00000580449.5 linkuse as main transcriptc.140C>T p.Pro47Leu missense_variant 1/51 ENSP00000462544.1 Q8WWW0-3

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151824
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000140
AC:
1
AN:
71416
Hom.:
0
AF XY:
0.0000240
AC XY:
1
AN XY:
41620
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000495
GnomAD4 exome
AF:
0.00000834
AC:
11
AN:
1319638
Hom.:
0
Cov.:
35
AF XY:
0.00000769
AC XY:
5
AN XY:
650444
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000105
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151824
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74136
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 12, 2021The c.140C>T (p.P47L) alteration is located in exon 1 (coding exon 1) of the RASSF5 gene. This alteration results from a C to T substitution at nucleotide position 140, causing the proline (P) at amino acid position 47 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.073
T;.;.
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.060
N
LIST_S2
Benign
0.78
T;T;T
M_CAP
Benign
0.046
D
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N;N;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Pathogenic
0.89
D
Sift4G
Benign
0.14
T;T;T
Polyphen
0.18
B;P;.
Vest4
0.14
MutPred
0.26
Gain of MoRF binding (P = 0.0726);Gain of MoRF binding (P = 0.0726);Gain of MoRF binding (P = 0.0726);
MVP
0.36
ClinPred
0.060
T
GERP RS
1.8
Varity_R
0.054
gMVP
0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs888516223; hg19: chr1-206681075; API