4-73576485-T-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000307439.10(RASSF6):c.863A>T(p.His288Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000007 in 1,428,264 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
RASSF6
ENST00000307439.10 missense
ENST00000307439.10 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 5.04
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]
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ACMG classification
Classification made for transcript
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 |
---|---|---|---|---|---|---|---|---|
RASSF6 | NM_177532.5 | c.863A>T | p.His288Leu | missense_variant | 10/11 | ENST00000307439.10 | NP_803876.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RASSF6 | ENST00000307439.10 | c.863A>T | p.His288Leu | missense_variant | 10/11 | 1 | NM_177532.5 | ENSP00000303877 | P1 | |
RASSF6 | ENST00000335049.5 | c.827A>T | p.His276Leu | missense_variant | 9/10 | 1 | ENSP00000335582 | |||
RASSF6 | ENST00000395777.6 | c.761A>T | p.His254Leu | missense_variant | 9/10 | 1 | ENSP00000379123 | |||
RASSF6 | ENST00000342081.7 | c.959A>T | p.His320Leu | missense_variant | 10/11 | 2 | ENSP00000340578 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 7.00e-7 AC: 1AN: 1428264Hom.: 0 Cov.: 28 AF XY: 0.00000141 AC XY: 1AN XY: 707724
GnomAD4 exome
AF:
AC:
1
AN:
1428264
Hom.:
Cov.:
28
AF XY:
AC XY:
1
AN XY:
707724
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 20, 2023 | The c.959A>T (p.H320L) alteration is located in exon 10 (coding exon 10) of the RASSF6 gene. This alteration results from a A to T substitution at nucleotide position 959, causing the histidine (H) at amino acid position 320 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Benign
DEOGEN2
Benign
.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
0.95, 0.94, 0.65
.;P;P;P
Vest4
MutPred
0.42
.;Gain of helix (P = 0.0854);.;.;
MVP
MPC
0.0082
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -31
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.