15-41417141-G-C

Variant names:

• chr15-41417141-G-C
• rs1395564368
• NM_015138.5:c.26G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_015138.5(RTF1):​c.26G>C​(p.Arg9Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,104,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: RTF1 NM_015138.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.34328288).
• BS2: High AC in GnomAdExome4 at 13 AD gene.

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>C	p.Arg9Pro	missense	Exon 1 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.26G>C	p.Arg9Pro	missense	Exon 1 of 18	ENSP00000374280.4	Q92541
	RTF1	ENST00000925186.1		c.26G>C	p.Arg9Pro	missense	Exon 1 of 17	ENSP00000595245.1
	RTF1	ENST00000925187.1		c.26G>C	p.Arg9Pro	missense	Exon 1 of 17	ENSP00000595246.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000118 AC: 13 AN: 1104926 Hom.: 0 Cov.: 31 AF XY: 0.0000114 AC XY: 6 AN XY: 525102

African (AFR) AF: 0.00 AC: 0 AN: 23032

American (AMR) AF: 0.00 AC: 0 AN: 8492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14444

East Asian (EAS) AF: 0.00 AC: 0 AN: 26816

South Asian (SAS) AF: 0.00 AC: 0 AN: 22102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3092

European-Non Finnish (NFE) AF: 0.0000140 AC: 13 AN: 928918

Other (OTH) AF: 0.00 AC: 0 AN: 44174

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.78	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.6
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.098	T
Polyphen		0.091	B
Vest4		0.47
MutPred		0.39		Loss of methylation at R9 (P = 2e-04)
MVP		0.25
MPC		1.6
ClinPred		0.69	D
GERP RS		2.7
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.21
gMVP		0.52
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs1395564368; hg19: chr15-41709339;