Genetic Variant RTF1:p.Thr40Asn (chr15-41417234-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_015138.5(RTF1):c.119C>A(p.Thr40Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RTF1
NM_015138.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.41

Variant links:

Genes affected

RTF1 (HGNC:28996): (RTF1 homolog, Paf1/RNA polymerase II complex component) This locus may represent a gene involved in regulation of transcription elongation and chromatin remodeling, based on studies of similar proteins in other organisms. The encoded protein may bind single-stranded DNA. [provided by RefSeq, Sep 2010]

RTF1 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=0.11544627).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTF1	NM_015138.5 link	c.119C>A	p.Thr40Asn	missense_variant	Exon 1 of 18	ENST00000389629.9	NP_055953.3	Q92541

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RTF1	ENST00000389629.9 link	c.119C>A	p.Thr40Asn	missense_variant	Exon 1 of 18	1	NM_015138.5	ENSP00000374280.4	Q92541
RTF1	ENST00000462276.1 link	n.103C>A		non_coding_transcript_exon_variant	Exon 1 of 4	4
RTF1	ENST00000558298.5 link	n.174+8653C>A		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1103660

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

523126

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.119C>A (p.T40N) alteration is located in exon 1 (coding exon 1) of the RTF1 gene. This alteration results from a C to A substitution at nucleotide position 119, causing the threonine (T) at amino acid position 40 to be replaced by an asparagine (N). 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

0.14

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.068

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.49

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.26

REVEL

Benign

0.060

Sift

Benign

0.039

Sift4G

Benign

0.46

Polyphen

0.063

Vest4

0.12

MutPred

0.26

Loss of sheet (P = 0.0037);

MVP

0.23

MPC

1.4

ClinPred

0.78

GERP RS

3.9

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.17

gMVP

0.15

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over