Variant 3-16377808-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015150.2(RFTN1):c.736G>C(p.Gly246Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

RFTN1
NM_015150.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

Variant links:

Genes affected

RFTN1 (HGNC:30278): (raftlin, lipid raft linker 1) Enables double-stranded RNA binding activity. Involved in B cell receptor signaling pathway; membrane raft assembly; and positive regulation of growth rate. Acts upstream of or within dsRNA transport; response to exogenous dsRNA; and toll-like receptor 3 signaling pathway. Located in endosome; membrane raft; and plasma membrane. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

RFTN1 links:

Genome browser will be placed here

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=0.08050385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFTN1	NM_015150.2 linkuse as main transcript	c.736G>C	p.Gly246Arg	missense_variant	5/10	ENST00000334133.9	NP_055965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RFTN1	ENST00000334133.9 linkuse as main transcript	c.736G>C	p.Gly246Arg	missense_variant	5/10	1	NM_015150.2	ENSP00000334153	P1
RFTN1	ENST00000432519.5 linkuse as main transcript	c.628G>C	p.Gly210Arg	missense_variant	4/9	1		ENSP00000403926
RFTN1	ENST00000451036.5 linkuse as main transcript	c.736G>C	p.Gly246Arg	missense_variant	5/5	4		ENSP00000403997

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000477

AC:

AN:

251428

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000347

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:

1461888

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000313

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.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

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

Oct 22, 2021

The c.736G>C (p.G246R) alteration is located in exon 5 (coding exon 4) of the RFTN1 gene. This alteration results from a G to C substitution at nucleotide position 736, causing the glycine (G) at amino acid position 246 to be replaced by an arginine (R). 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

0.095

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.090

.;T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.081

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

.;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.079

Sift

Benign

0.22

T;T;D

Sift4G

Benign

0.26

T;T;D

Polyphen

0.85

P;P;.

Vest4

0.21

MutPred

0.14

.;Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);

MVP

0.42

MPC

0.54

ClinPred

0.16

GERP RS

3.5

Varity_R

0.021

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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