12-64609189-T-G

Variant names:

• chr12-64609189-T-G
• rs6581580
• ENST00000637125.1:c.294+67484T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000546135.1(RASSF3-DT):​n.115+156A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,624 control chromosomes in the GnomAD database, including 15,480 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (15480 hom., cov: 30)
• Consequence: RASSF3-DT ENST00000546135.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419
• Publications: 10 publications found

Genes affected

RASSF3 (HGNC:14271): (Ras association domain family member 3) The RAS oncogene (MIM 190020) is mutated in nearly one-third of all human cancers. Members of the RAS superfamily are plasma membrane GTP-binding proteins that modulate intracellular signal transduction pathways. A subfamily of RAS effectors, including RASSF3, share a RAS association (RA) domain.[supplied by OMIM, Jul 2003]

RASSF3-DT (HGNC:55489): (RASSF3 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000546135.1. 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
	RASSF3-DT	NR_187549.1		n.122+156A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASSF3	ENST00000637125.1	TSL:5	c.294+67484T>G		intron	N/A	ENSP00000490100.1	A0A1B0GUG6
	RASSF3-DT	ENST00000546135.1	TSL:3	n.115+156A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67293 AN: 151506 Hom.: 15456 Cov.: 30

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.432

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.444 AC: 67356 AN: 151624 Hom.: 15480 Cov.: 30 AF XY: 0.439 AC XY: 32508 AN XY: 74082

African (AFR) AF: 0.526 AC: 21729 AN: 41288

American (AMR) AF: 0.440 AC: 6678 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1501 AN: 3472

East Asian (EAS) AF: 0.198 AC: 1022 AN: 5152

South Asian (SAS) AF: 0.362 AC: 1731 AN: 4786

European-Finnish (FIN) AF: 0.383 AC: 4027 AN: 10504

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29320 AN: 67918

Other (OTH) AF: 0.435 AC: 917 AN: 2110

Alfa AF: 0.430 Hom.: 15680

Bravo AF: 0.451

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.67
PhyloP100		-0.42

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6581580;

hg19: chr12-65002969;