Variant chr1-206507804-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_182663.4(RASSF5):c.202G>T(p.Gly68Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000332 in 1,398,482 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

RASSF5
NM_182663.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

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:

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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=0.004478842).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASSF5	NM_182663.4 linkuse as main transcript	c.202G>T	p.Gly68Trp	missense_variant	1/6	ENST00000579436.7	NP_872604.1	Q8WWW0-1A8K5F3
RASSF5	NM_182664.4 linkuse as main transcript	c.202G>T	p.Gly68Trp	missense_variant	1/5		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.202G>T	p.Gly68Trp	missense_variant	1/6	1	NM_182663.4	ENSP00000462099.1	Q8WWW0-1
RASSF5	ENST00000581503.6 linkuse as main transcript	c.202G>T	p.Gly68Trp	missense_variant	1/4	1		ENSP00000464039.2	A0A075B763
RASSF5	ENST00000580449.5 linkuse as main transcript	c.202G>T	p.Gly68Trp	missense_variant	1/5	1		ENSP00000462544.1	Q8WWW0-3

Frequencies

GnomAD3 genomes

AF:

0.00187

AC:

283

AN:

151500

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00671

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000295

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000115

AC:

AN:

25996

Hom.:

AF XY:

0.000124

AC XY:

AN XY:

16176

show subpopulations

Gnomad AFR exome

AF:

0.00698

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:

0.00

GnomAD4 exome

AF:

0.000145

AC:

181

AN:

1246878

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

AN XY:

611126

show subpopulations

Gnomad4 AFR exome

AF:

0.00662

Gnomad4 AMR exome

AF:

0.000147

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:

0.00

Gnomad4 OTH exome

AF:

0.000311

GnomAD4 genome

AF:

0.00187

AC:

283

AN:

151604

Hom.:

Cov.:

AF XY:

0.00190

AC XY:

141

AN XY:

74100

show subpopulations

Gnomad4 AFR

AF:

0.00670

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000925

Hom.:

Bravo

AF:

0.00190

ExAC

AF:

0.0000423

AC:

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

Mar 06, 2023

The c.202G>T (p.G68W) alteration is located in exon 1 (coding exon 1) of the RASSF5 gene. This alteration results from a G to T substitution at nucleotide position 202, causing the glycine (G) at amino acid position 68 to be replaced by a tryptophan (W). 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

0.19

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.065

T;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.72

T;T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.0045

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;L;.

PrimateAI

Pathogenic

0.89

Sift4G

Uncertain

0.020

D;D;D

Polyphen

0.96

D;D;.

Vest4

0.35

MutPred

0.27

Loss of methylation at R67 (P = 0.0222);Loss of methylation at R67 (P = 0.0222);Loss of methylation at R67 (P = 0.0222);

MVP

0.36

ClinPred

0.14

GERP RS

1.5

Varity_R

0.051

gMVP

0.39

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