4-73576485-T-A

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

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.04
Variant links:
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]

Genome browser will be placed here

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
RASSF6NM_177532.5 linkuse as main transcriptc.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
RASSF6ENST00000307439.10 linkuse as main transcriptc.863A>T p.His288Leu missense_variant 10/111 NM_177532.5 ENSP00000303877 P1Q6ZTQ3-2
RASSF6ENST00000335049.5 linkuse as main transcriptc.827A>T p.His276Leu missense_variant 9/101 ENSP00000335582 Q6ZTQ3-3
RASSF6ENST00000395777.6 linkuse as main transcriptc.761A>T p.His254Leu missense_variant 9/101 ENSP00000379123 Q6ZTQ3-4
RASSF6ENST00000342081.7 linkuse as main transcriptc.959A>T p.His320Leu missense_variant 10/112 ENSP00000340578 Q6ZTQ3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.00e-7
AC:
1
AN:
1428264
Hom.:
0
Cov.:
28
AF XY:
0.00000141
AC XY:
1
AN XY:
707724
show subpopulations
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:
9.14e-7
Gnomad4 OTH exome
AF:
0.00
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 submitterclinical testingAmbry GeneticsSep 20, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Benign
-0.035
T
BayesDel_noAF
Benign
-0.29
CADD
Pathogenic
28
DANN
Benign
0.97
DEOGEN2
Benign
0.033
.;T;.;.
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.81
T;T;T;T
M_CAP
Benign
0.024
T
MetaRNN
Uncertain
0.65
D;D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
.;M;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Benign
0.46
T
PROVEAN
Pathogenic
-5.3
D;D;D;D
REVEL
Benign
0.14
Sift
Uncertain
0.0030
D;D;D;D
Sift4G
Uncertain
0.0070
D;D;D;D
Polyphen
0.95, 0.94, 0.65
.;P;P;P
Vest4
0.58
MutPred
0.42
.;Gain of helix (P = 0.0854);.;.;
MVP
0.60
MPC
0.0082
ClinPred
0.99
D
GERP RS
6.1
Varity_R
0.42
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.24
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.24
Position offset: -31

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: chr4-74442202; API