rs143969358

Variant names:

• chr4-73587909-C-G
• rs143969358
• NM_177532.5:c.313G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-73587909-C-G
• chr4-73587909-C-A
• chr4-73587909-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_177532.5(RASSF6):​c.313G>C​(p.Asp105His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,150 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RASSF6 NM_177532.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.41
• Publications: 6 publications found

Genes affected

RASSF6 (HGNC:20796): (Ras association domain family member 6) This gene encodes a member of the Ras-association domain family (RASSF). Members of this family form the core of a highly conserved tumor suppressor network, the Salvador-Warts-Hippo (SWH) pathway. The protein encoded by this gene is a Ras effector protein that induces apoptosis. A genomic region containing this gene has been linked to susceptibility to viral bronchiolitis. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177532.5. 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
	RASSF6	NM_177532.5	MANE Select	c.313G>C	p.Asp105His	missense	Exon 5 of 11	NP_803876.1	Q6ZTQ3-2
	RASSF6	NM_201431.2		c.409G>C	p.Asp137His	missense	Exon 5 of 11	NP_958834.1	Q6ZTQ3-1
	RASSF6	NM_001270392.1		c.277G>C	p.Asp93His	missense	Exon 4 of 10	NP_001257321.1	Q6ZTQ3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASSF6	ENST00000307439.10	TSL:1 MANE Select	c.313G>C	p.Asp105His	missense	Exon 5 of 11	ENSP00000303877.5	Q6ZTQ3-2
	RASSF6	ENST00000335049.5	TSL:1	c.277G>C	p.Asp93His	missense	Exon 4 of 10	ENSP00000335582.5	Q6ZTQ3-3
	RASSF6	ENST00000395777.6	TSL:1	c.313G>C	p.Asp105His	missense	Exon 5 of 10	ENSP00000379123.2	Q6ZTQ3-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457150 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 725004

African (AFR) AF: 0.00 AC: 0 AN: 33356

American (AMR) AF: 0.00 AC: 0 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26000

East Asian (EAS) AF: 0.00 AC: 0 AN: 39550

South Asian (SAS) AF: 0.00 AC: 0 AN: 85930

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108520

Other (OTH) AF: 0.00 AC: 0 AN: 60118

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000179 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.22
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.026	D
Polyphen		1.0	D
Vest4		0.70
MVP		0.35
MPC		0.018
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.40
gMVP		0.58
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs143969358; hg19: chr4-74453626;