Variant chr3-50340624-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_007182.5(RASSF1):c.182C>G(p.Thr61Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,380,406 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: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RASSF1
NM_007182.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.12

Variant links:

Genes affected

RASSF1 (HGNC:9882): (Ras association domain family member 1) This gene encodes a protein similar to the RAS effector proteins. Loss or altered expression of this gene has been associated with the pathogenesis of a variety of cancers, which suggests the tumor suppressor function of this gene. The inactivation of this gene was found to be correlated with the hypermethylation of its CpG-island promoter region. The encoded protein was found to interact with DNA repair protein XPA. The protein was also shown to inhibit the accumulation of cyclin D1, and thus induce cell cycle arrest. Several alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, May 2011]

RASSF1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31341404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RASSF1	NM_007182.5 linkuse as main transcript	c.182C>G	p.Thr61Arg	missense_variant	1/6	ENST00000359365.9	NP_009113.3
RASSF1	NM_170714.2 linkuse as main transcript	c.182C>G	p.Thr61Arg	missense_variant	1/6		NP_733832.1
RASSF1	NM_001206957.2 linkuse as main transcript	c.-165C>G		5_prime_UTR_variant	1/5		NP_001193886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASSF1	ENST00000359365.9 linkuse as main transcript	c.182C>G	p.Thr61Arg	missense_variant	1/6	1	NM_007182.5	ENSP00000352323	P1	Q9NS23-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1380406

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

683754

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:

9.24e-7

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Mar 31, 2022

The c.182C>G (p.T61R) alteration is located in exon 1 (coding exon 1) of the RASSF1 gene. This alteration results from a C to G substitution at nucleotide position 182, causing the threonine (T) at amino acid position 61 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.066

T;.

Eigen

Benign

0.0091

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.81

T;T

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.31

T;T

MetaSVM

Uncertain

0.16

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

0.88

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.52

N;N

REVEL

Uncertain

0.55

Sift

Benign

0.40

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.69

P;B

Vest4

0.40

MutPred

0.31

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.99

MPC

0.41

ClinPred

0.78

GERP RS

5.2

Varity_R

0.24

gMVP

0.32

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