3-50337275-G-C

Variant names:

• chr3-50337275-G-C
• rs149932910
• ENST00000327761.7:c.45C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_170713.3(RASSF1):​c.45C>G​(p.Ser15Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S15S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RASSF1 NM_170713.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.28
• 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]

RASSF1-AS1 (HGNC:49091): (RASSF1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34972376).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170713.3. 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.357+630C>G		intron	N/A	NP_009113.3
	RASSF1	NM_170713.3		c.45C>G	p.Ser15Arg	missense	Exon 1 of 5	NP_733831.1	Q9NS23-4
	RASSF1	NM_170714.2		c.369+630C>G		intron	N/A	NP_733832.1	Q9NS23-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASSF1	ENST00000327761.7	TSL:1	c.45C>G	p.Ser15Arg	missense	Exon 1 of 5	ENSP00000333327.3	Q9NS23-4
	RASSF1	ENST00000359365.9	TSL:1 MANE Select	c.357+630C>G		intron	N/A	ENSP00000352323.4	Q9NS23-2
	RASSF1	ENST00000357043.6	TSL:1	c.369+630C>G		intron	N/A	ENSP00000349547.2	Q9NS23-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460768 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726694

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.0000224 AC: 1 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111708

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	1.0
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
PhyloP100		7.3
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.087
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.070	T
Vest4		0.49
MutPred		0.15		Gain of glycosylation at S18 (P = 0.0342)
MVP		0.41
ClinPred		0.95	D
GERP RS		4.8
PromoterAI		0.10	Neutral
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs149932910; hg19: chr3-50374706;