1-206507967-G-A

Position:

• chr1-206507967-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182663.4(RASSF5):​c.365G>A​(p.Gly122Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RASSF5 NM_182663.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.19

Genes affected

RASSF5 (HGNC:17609): (Ras association domain family member 5) This gene is a member of the Ras association domain family. It functions as a tumor suppressor, and is inactivated in a variety of cancers. The encoded protein localizes to centrosomes and microtubules, and associates with the GTP-activated forms of Ras, Rap1, and several other Ras-like small GTPases. The protein regulates lymphocyte adhesion and suppresses cell growth in response to activated Rap1 or Ras. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASSF5	NM_182663.4	c.365G>A	p.Gly122Glu	missense_variant	1/6	ENST00000579436.7	NP_872604.1
RASSF5	NM_182664.4	c.365G>A	p.Gly122Glu	missense_variant	1/5		NP_872605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASSF5	ENST00000579436.7	c.365G>A	p.Gly122Glu	missense_variant	1/6	1	NM_182663.4	ENSP00000462099.1
RASSF5	ENST00000581503.6	c.365G>A	p.Gly122Glu	missense_variant	1/4	1		ENSP00000464039.2
RASSF5	ENST00000580449.5	c.365G>A	p.Gly122Glu	missense_variant	1/5	1		ENSP00000462544.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1384030 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 685462

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 21, 2024

The c.365G>A (p.G122E) alteration is located in exon 1 (coding exon 1) of the RASSF5 gene. This alteration results from a G to A substitution at nucleotide position 365, causing the glycine (G) at amino acid position 122 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;.;.
Eigen	Benign	0.079
Eigen_PC	Benign	0.072
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Pathogenic	0.87	D
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Benign	0.90	L;L;.
PrimateAI	Pathogenic	0.90	D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		0.11	B;D;.
Vest4		0.41
MutPred		0.35		Loss of methylation at R119 (P = 0.0956);Loss of methylation at R119 (P = 0.0956);Loss of methylation at R119 (P = 0.0956);
MVP		0.83
ClinPred		0.95	D
GERP RS		3.8
Varity_R		0.22
gMVP		0.49

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-206681300;