1-206507747-C-A

Position:

• chr1-206507747-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182663.4(RASSF5):​c.145C>A​(p.Pro49Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RASSF5 NM_182663.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.42

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07868546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASSF5	NM_182663.4	c.145C>A	p.Pro49Thr	missense_variant	1/6	ENST00000579436.7	NP_872604.1
RASSF5	NM_182664.4	c.145C>A	p.Pro49Thr	missense_variant	1/5		NP_872605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASSF5	ENST00000579436.7	c.145C>A	p.Pro49Thr	missense_variant	1/6	1	NM_182663.4	ENSP00000462099.1
RASSF5	ENST00000581503.6	c.145C>A	p.Pro49Thr	missense_variant	1/4	1		ENSP00000464039.2
RASSF5	ENST00000580449.5	c.145C>A	p.Pro49Thr	missense_variant	1/5	1		ENSP00000462544.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

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

Apr 20, 2023

The c.145C>A (p.P49T) alteration is located in exon 1 (coding exon 1) of the RASSF5 gene. This alteration results from a C to A substitution at nucleotide position 145, causing the proline (P) at amino acid position 49 to be replaced by a threonine (T). 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	Benign	0.073
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.6
DANN	Benign	0.95
DEOGEN2	Benign	0.051	T;.;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.079	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;.
PrimateAI	Pathogenic	0.84	D
Sift4G	Benign	0.28	T;T;T
Polyphen		0.041	B;B;.
Vest4		0.043
MutPred		0.13		Gain of phosphorylation at P49 (P = 0.0257);Gain of phosphorylation at P49 (P = 0.0257);Gain of phosphorylation at P49 (P = 0.0257);
MVP		0.30
ClinPred		0.12	T
GERP RS		1.8
Varity_R		0.028
gMVP		0.41

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: chr1-206681080;