rs782164646

Variant names:

• chr3-50330721-C-G
• rs782164646
• 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. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A295T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RASSF1 NM_007182.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.88
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007182.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASSF1	NM_007182.5	MANE Select	c.883G>C	p.Ala295Pro	missense	Exon 6 of 6	NP_009113.3
	RASSF1	NM_170714.2		c.895G>C	p.Ala299Pro	missense	Exon 6 of 6	NP_733832.1	Q9NS23-1
	RASSF1	NM_170713.3		c.673G>C	p.Ala225Pro	missense	Exon 5 of 5	NP_733831.1	Q9NS23-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASSF1	ENST00000359365.9	TSL:1 MANE Select	c.883G>C	p.Ala295Pro	missense	Exon 6 of 6	ENSP00000352323.4	Q9NS23-2
	RASSF1	ENST00000357043.6	TSL:1	c.895G>C	p.Ala299Pro	missense	Exon 6 of 6	ENSP00000349547.2	Q9NS23-1
	RASSF1	ENST00000327761.7	TSL:1	c.673G>C	p.Ala225Pro	missense	Exon 5 of 5	ENSP00000333327.3	Q9NS23-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.9
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	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
Mutation Taster		=16/84	disease causing

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

Other links and lift over

dbSNP: rs782164646; hg19: chr3-50368152; COSMIC: COSV99222758; COSMIC: COSV99222758;