17-59960156-T-C

Position:

• chr17-59960156-T-C

Variant summary

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

The NM_016125.4(RNFT1):​c.604A>G​(p.Lys202Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000413 in 1,451,562 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: RNFT1 NM_016125.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.63

Genes affected

RNFT1 (HGNC:30206): (ring finger protein, transmembrane 1) Enables ubiquitin binding activity and ubiquitin protein ligase activity. Involved in positive regulation of ERAD pathway and protein autoubiquitination. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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
RNFT1	NM_016125.4	c.604A>G	p.Lys202Glu	missense_variant	4/9	ENST00000305783.13	NP_057209.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNFT1	ENST00000305783.13	c.604A>G	p.Lys202Glu	missense_variant	4/9	1	NM_016125.4	ENSP00000304670	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000413 AC: 6 AN: 1451562 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 721800

Gnomad4 AFR exome AF: 0.0000304

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: 0.00000451

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Dec 02, 2022

The c.604A>G (p.K202E) alteration is located in exon 4 (coding exon 4) of the RNFT1 gene. This alteration results from a A to G substitution at nucleotide position 604, causing the lysine (K) at amino acid position 202 to be replaced by a glutamic acid (E). 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	0.19
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	0.94	D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.7	N;.
REVEL	Benign	0.15
Sift	Benign	0.24	T;.
Sift4G	Benign	0.20	T;T
Polyphen		0.92	P;.
Vest4		0.69
MutPred		0.47		Loss of ubiquitination at K202 (P = 0.0362);.;
MVP		0.45
MPC		0.62
ClinPred		0.95	D
GERP RS		5.0
Varity_R		0.30
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr17-58037517;