rs782164646

Variant names:

• chr3-50330721-C-G
• NM_007182.5:c.883G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-50330721-C-G
• chr3-50330721-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_007182.5(RASSF1):​c.883G>C​(p.Ala295Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RASSF1 NM_007182.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.88

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASSF1	NM_007182.5	c.883G>C	p.Ala295Pro	missense_variant	Exon 6 of 6	ENST00000359365.9	NP_009113.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASSF1	ENST00000359365.9	c.883G>C	p.Ala295Pro	missense_variant	Exon 6 of 6	1	NM_007182.5	ENSP00000352323.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	.;.;.;D;.
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D;.;D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.80	D;D;D;D;D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Pathogenic	3.0	.;.;.;M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-4.5	D;.;D;D;D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0030	D;.;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D;D
Polyphen		1.0, 0.98	.;.;.;D;D
Vest4		0.77
MutPred		0.47		.;.;.;Gain of disorder (P = 0.0429);.;
MVP		0.98
MPC		1.3
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.97
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-50368152; COSMIC: COSV99222758; COSMIC: COSV99222758;