Variant 4-73593496-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000307439.10(RASSF6):c.242C>T(p.Ser81Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

RASSF6
ENST00000307439.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.25

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]

RASSF6 links:

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ACMG classification

Classification made for transcript

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=0.1800848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASSF6	NM_177532.5 linkuse as main transcript	c.242C>T	p.Ser81Phe	missense_variant	4/11	ENST00000307439.10	NP_803876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASSF6	ENST00000307439.10 linkuse as main transcript	c.242C>T	p.Ser81Phe	missense_variant	4/11	1	NM_177532.5	ENSP00000303877	P1	Q6ZTQ3-2
RASSF6	ENST00000335049.5 linkuse as main transcript	c.206C>T	p.Ser69Phe	missense_variant	3/10	1		ENSP00000335582		Q6ZTQ3-3
RASSF6	ENST00000395777.6 linkuse as main transcript	c.242C>T	p.Ser81Phe	missense_variant	4/10	1		ENSP00000379123		Q6ZTQ3-4
RASSF6	ENST00000342081.7 linkuse as main transcript	c.338C>T	p.Ser113Phe	missense_variant	4/11	2		ENSP00000340578		Q6ZTQ3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000439

AC:

AN:

250802

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135558

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000320

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461324

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000314

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.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 29, 2022

The c.338C>T (p.S113F) alteration is located in exon 4 (coding exon 4) of the RASSF6 gene. This alteration results from a C to T substitution at nucleotide position 338, causing the serine (S) at amino acid position 113 to be replaced by a phenylalanine (F). 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

0.099

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0031

.;T;.;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.062

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.74

T;T;T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

.;L;.;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.049

Sift

Uncertain

0.0040

D;T;D;T

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.0070, 0.0020, 0.0010

.;B;B;B

Vest4

0.37

MutPred

0.34

.;Gain of glycosylation at S117 (P = 0.0052);.;.;

MVP

0.39

MPC

0.0044

ClinPred

0.17

GERP RS

5.4

Varity_R

0.095

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over