rs764575533

Variant names:

• chr15-41518082-C-A
• rs764575533
• NM_015540.4:c.3896G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-41518082-C-A
• chr15-41518082-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015540.4(RPAP1):​c.3896G>T​(p.Arg1299Leu) 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. 14/21 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. R1299H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPAP1 NM_015540.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.64

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

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=0.09566218).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPAP1	NM_015540.4	c.3896G>T	p.Arg1299Leu	missense_variant	Exon 23 of 25	ENST00000304330.9	NP_056355.2
RPAP1	XM_005254297.2	c.3896G>T	p.Arg1299Leu	missense_variant	Exon 23 of 25		XP_005254354.1
RPAP1	XM_047432374.1	c.3716G>T	p.Arg1239Leu	missense_variant	Exon 22 of 24		XP_047288330.1
RPAP1	XM_047432375.1	c.3716G>T	p.Arg1239Leu	missense_variant	Exon 22 of 24		XP_047288331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPAP1	ENST00000304330.9	c.3896G>T	p.Arg1299Leu	missense_variant	Exon 23 of 25	1	NM_015540.4	ENSP00000306123.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.10
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.037
Sift	Benign	0.17	T
Sift4G	Benign	0.23	T
Polyphen		0.0	B
Vest4		0.34
MutPred		0.48		Loss of helix (P = 0.0558);
MVP		0.12
MPC		0.26
ClinPred		0.13	T
GERP RS		-5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.038
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs764575533; hg19: chr15-41810280;