15-41520636-C-A

Variant names:

• chr15-41520636-C-A
• rs184673233
• NM_015540.4:c.3550G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015540.4(RPAP1):​c.3550G>T​(p.Ala1184Ser) 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. 17/22 in silico tools predict 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. A1184T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPAP1 NM_015540.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.38
• Publications: 1 publications found

Genes affected

RPAP1 (HGNC:24567): (RNA polymerase II associated protein 1) This protein forms part of the RNA polymerase II (RNAPII) enzyme complex and may recruit RNAPII to chromatin through its interaction with acetylated histones. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.103762805).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015540.4. 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
	RPAP1	NM_015540.4	MANE Select	c.3550G>T	p.Ala1184Ser	missense	Exon 22 of 25	NP_056355.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPAP1	ENST00000304330.9	TSL:1 MANE Select	c.3550G>T	p.Ala1184Ser	missense	Exon 22 of 25	ENSP00000306123.4	Q9BWH6-1
	RPAP1	ENST00000562303.5	TSL:1	n.3550G>T		non_coding_transcript_exon	Exon 22 of 24	ENSP00000455363.1	Q9BWH6-2
	RPAP1	ENST00000565167.1	TSL:1	n.566G>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.4
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.16
Sift	Benign	0.20	T
Sift4G	Benign	0.59	T
Polyphen		0.29	B
Vest4		0.11
MutPred		0.34		Gain of relative solvent accessibility (P = 0.0215)
MVP		0.66
MPC		0.50
ClinPred		0.78	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.035
gMVP		0.13

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: rs184673233; hg19: chr15-41812834;