15-41470365-G-C

Variant names:

• chr15-41470365-G-C
• rs201424243
• NM_015138.5:c.998G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015138.5(RTF1):​c.998G>C​(p.Arg333Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R333Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RTF1 NM_015138.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.998G>C	p.Arg333Pro	missense	Exon 7 of 18	NP_055953.3	Q92541

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTF1	ENST00000389629.9	TSL:1 MANE Select	c.998G>C	p.Arg333Pro	missense	Exon 7 of 18	ENSP00000374280.4	Q92541
	RTF1	ENST00000925186.1		c.998G>C	p.Arg333Pro	missense	Exon 7 of 17	ENSP00000595245.1
	RTF1	ENST00000925187.1		c.887G>C	p.Arg296Pro	missense	Exon 6 of 17	ENSP00000595246.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461724 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727166

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111888

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0079	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.69	N
PhyloP100		9.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.21
Sift	Benign	0.23	T
Sift4G	Benign	0.26	T
Polyphen		1.0	D
Vest4		0.64
MutPred		0.17		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.37
MPC		1.8
ClinPred		0.57	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.39
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201424243; hg19: chr15-41762563;