3-16377752-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015150.2(RFTN1):c.792C>A(p.Asn264Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000027 (0 hom.)
• Consequence: RFTN1 NM_015150.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33

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]

ACMG classification

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=0.08251205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFTN1	NM_015150.2	c.792C>A	p.Asn264Lys	missense_variant	5/10	ENST00000334133.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFTN1	ENST00000334133.9	c.792C>A	p.Asn264Lys	missense_variant	5/10	1	NM_015150.2	P1
RFTN1	ENST00000432519.5	c.684C>A	p.Asn228Lys	missense_variant	4/9	1
RFTN1	ENST00000451036.5	c.792C>A	p.Asn264Lys	missense_variant	5/5	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1456712 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 723462

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.792C>A (p.N264K) alteration is located in exon 5 (coding exon 4) of the RFTN1 gene. This alteration results from a C to A substitution at nucleotide position 792, causing the asparagine (N) at amino acid position 264 to be replaced by a lysine (K). 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	0.12
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	8.6
Dann	Benign	0.72
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.51	T;T;T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.083	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.88	N;N;N
REVEL	Benign	0.071
Sift	Benign	0.041	D;D;D
Sift4G	Benign	0.26	T;T;T
Polyphen		0.0080	B;B;.
Vest4		0.14
MutPred		0.28		.;Gain of ubiquitination at N264 (P = 0);Gain of ubiquitination at N264 (P = 0);
MVP		0.29
MPC		0.13
ClinPred		0.18	T
GERP RS		4.4
Varity_R		0.045
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-16419259;