Genetic Variant RTF1:p.Arg9Leu (chr15-41417141-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_015138.5(RTF1):c.26G>T(p.Arg9Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R9P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RTF1
NM_015138.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.57

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27474284).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015138.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTF1	NM_015138.5	MANE Select	c.26G>T	p.Arg9Leu	missense	Exon 1 of 18	NP_055953.3	Q92541

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RTF1	ENST00000389629.9	TSL:1 MANE Select	c.26G>T	p.Arg9Leu	missense	Exon 1 of 18	ENSP00000374280.4	Q92541
RTF1	ENST00000925186.1		c.26G>T	p.Arg9Leu	missense	Exon 1 of 17	ENSP00000595245.1
RTF1	ENST00000925187.1		c.26G>T	p.Arg9Leu	missense	Exon 1 of 17	ENSP00000595246.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1104924

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

525100

African (AFR)

AF:

0.00

AC:

AN:

23032

American (AMR)

AF:

0.00

AC:

AN:

8492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14444

East Asian (EAS)

AF:

0.00

AC:

AN:

26816

South Asian (SAS)

AF:

0.00

AC:

AN:

22100

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33856

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3092

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

928918

Other (OTH)

AF:

0.00

AC:

AN:

44174

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152064

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41418

American (AMR)

AF:

0.0000655

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.079

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.070

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.62

M_CAP

Pathogenic

0.80

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

4.6

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.17

REVEL

Benign

0.16

Sift

Pathogenic

0.0

Sift4G

Benign

0.11

Polyphen

0.010

Vest4

0.40

MutPred

0.40

Loss of methylation at R9 (P = 2e-04)

MVP

0.13

MPC

1.4

ClinPred

0.69

GERP RS

2.7

PromoterAI

-0.050

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.24

gMVP

0.52

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over