chr12-64662602-A-T

Variant names:

• chr12-64662602-A-T
• rs10506536
• NM_178169.4:c.112-22185A>T

Variant summary

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

The NM_178169.4(RASSF3):​c.112-22185A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0639 in 152,172 control chromosomes in the GnomAD database, including 1,053 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 0.064 (1053 hom., cov: 31)
• Consequence: RASSF3 NM_178169.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 0 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178169.4. 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	NM_178169.4	MANE Select	c.112-22185A>T		intron	N/A	NP_835463.1	Q86WH2-1
	RASSF3	NR_040718.2		n.250-22185A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASSF3	ENST00000542104.6	TSL:1 MANE Select	c.112-22185A>T		intron	N/A	ENSP00000443021.1	Q86WH2-1
	RASSF3	ENST00000637125.1	TSL:5	c.295-22185A>T		intron	N/A	ENSP00000490100.1	A0A1B0GUG6
	RASSF3	ENST00000899845.1		c.112-22185A>T		intron	N/A	ENSP00000569904.1

Frequencies

GnomAD3 genomes AF: 0.0638 AC: 9697 AN: 152054 Hom.: 1051 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.0373

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

GnomAD4 genome AF: 0.0639 AC: 9725 AN: 152172 Hom.: 1053 Cov.: 31 AF XY: 0.0619 AC XY: 4607 AN XY: 74410

African (AFR) AF: 0.223 AC: 9242 AN: 41462

American (AMR) AF: 0.0225 AC: 344 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000794 AC: 54 AN: 68022

Other (OTH) AF: 0.0369 AC: 78 AN: 2112

Alfa AF: 0.0485 Hom.: 69

Bravo AF: 0.0714

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.82
DANN	Benign	0.83
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10506536; hg19: chr12-65056382;