chr1-206538247-G-A

Position:

chr1-206538247-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000579436.7(RASSF5):c.533G>A(p.Arg178Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

RASSF5
ENST00000579436.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.884

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]

RASSF5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055302024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASSF5	NM_182663.4 linkuse as main transcript	c.533G>A	p.Arg178Gln	missense_variant	2/6	ENST00000579436.7	NP_872604.1	Q8WWW0-1A8K5F3
RASSF5	NM_182664.4 linkuse as main transcript	c.533G>A	p.Arg178Gln	missense_variant	2/5		NP_872605.1	Q8WWW0-3A8K5F3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RASSF5	ENST00000579436.7 linkuse as main transcript	c.533G>A	p.Arg178Gln	missense_variant	2/6	1	NM_182663.4	ENSP00000462099.1	Q8WWW0-1
RASSF5	ENST00000581503.6 linkuse as main transcript	c.533G>A	p.Arg178Gln	missense_variant	2/4	1		ENSP00000464039.2	A0A075B763
RASSF5	ENST00000580449.5 linkuse as main transcript	c.533G>A	p.Arg178Gln	missense_variant	2/5	1		ENSP00000462544.1	Q8WWW0-3
RASSF5	ENST00000636182.1 linkuse as main transcript	c.233G>A	p.Arg78Gln	missense_variant	2/6	5		ENSP00000489689.1	A0A1B0GTG4

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251476

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.000121

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.533G>A (p.R178Q) alteration is located in exon 2 (coding exon 2) of the RASSF5 gene. This alteration results from a G to A substitution at nucleotide position 533, causing the arginine (R) at amino acid position 178 to be replaced by a glutamine (Q). 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

0.064

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.49

DANN

Benign

0.86

DEOGEN2

Benign

0.043

T;.;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.66

T;T;T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.055

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

L;L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.19

Sift4G

Benign

0.59

T;T;T;.

Polyphen

0.0020

B;B;.;.

Vest4

0.085

MutPred

0.17

Gain of glycosylation at P181 (P = 0.226);Gain of glycosylation at P181 (P = 0.226);Gain of glycosylation at P181 (P = 0.226);.;

MVP

0.20

ClinPred

0.032

GERP RS

-2.0

Varity_R

0.019

gMVP

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over