17-59963203-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_016125.4(RNFT1):c.138C>T(p.His46=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00703 in 1,614,142 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0071 (42 hom.)
• Consequence: RNFT1 NM_016125.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.40

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]

TBC1D3P1-DHX40P1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 17-59963203-G-A is Benign according to our data. Variant chr17-59963203-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2647991.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.4 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNFT1	NM_016125.4	c.138C>T	p.His46=	synonymous_variant	2/9	ENST00000305783.13
TBC1D3P1-DHX40P1	NR_002924.3	n.1288C>T		non_coding_transcript_exon_variant	13/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNFT1	ENST00000305783.13	c.138C>T	p.His46=	synonymous_variant	2/9	1	NM_016125.4	P1

Frequencies

GnomAD3 genomes AF: 0.00594 AC: 904 AN: 152192 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00595

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00800

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00922

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00607 AC: 1522 AN: 250714 Hom.: 8 AF XY: 0.00609 AC XY: 826 AN XY: 135616

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.00387

Gnomad ASJ exome AF: 0.00655

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00327

Gnomad FIN exome AF: 0.00763

Gnomad NFE exome AF: 0.00872

Gnomad OTH exome AF: 0.00897

GnomAD4 exome AF: 0.00714 AC: 10444 AN: 1461832 Hom.: 42 Cov.: 31 AF XY: 0.00707 AC XY: 5143 AN XY: 727222

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.00409

Gnomad4 ASJ exome AF: 0.00700

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00312

Gnomad4 FIN exome AF: 0.00661

Gnomad4 NFE exome AF: 0.00801

Gnomad4 OTH exome AF: 0.00730

GnomAD4 genome AF: 0.00593 AC: 903 AN: 152310 Hom.: 5 Cov.: 31 AF XY: 0.00642 AC XY: 478 AN XY: 74492

Gnomad4 AFR AF: 0.00128

Gnomad4 AMR AF: 0.00595

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.00800

Gnomad4 NFE AF: 0.00922

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00851 Hom.: 1

Bravo AF: 0.00559

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0103

EpiControl AF: 0.00871

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

RNFT1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	6.5
Dann	Benign	0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs61751975; hg19: chr17-58040564;