chr18-36030845-T-C

Position:

• chr18-36030845-T-C

Variant summary

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

The NM_018170.5(RPRD1A):​c.449A>G​(p.Asn150Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RPRD1A NM_018170.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.16

Genes affected

RPRD1A (HGNC:25560): (regulation of nuclear pre-mRNA domain containing 1A) This gene encodes a cell-cycle and transcription regulatory protein. The encoded protein interacts with the cell cycle inhibitor cyclin-dependent kinase 4 inhibitor B and may function as a negative regulator of G(1)/S phase progression. This protein also forms homo- and hetrodimers with the protein, regulation of nuclear pre-mRNA domain-containing protein 1B, to form a scaffold that interacts with the C-terminal domain of RNA polymerase II subunit B1 and regulates several aspects of transcription. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 16. [provided by RefSeq, Dec 2014]

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=0.09109029).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPRD1A	NM_018170.5	c.449A>G	p.Asn150Ser	missense_variant	4/7	ENST00000399022.9	NP_060640.2
RPRD1A	NM_001303413.2	c.449A>G	p.Asn150Ser	missense_variant	4/7		NP_001290342.1
RPRD1A	NM_001303411.2	c.341A>G	p.Asn114Ser	missense_variant	5/8		NP_001290340.1
RPRD1A	NM_001303412.2	c.341A>G	p.Asn114Ser	missense_variant	5/9		NP_001290341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPRD1A	ENST00000399022.9	c.449A>G	p.Asn150Ser	missense_variant	4/7	1	NM_018170.5	ENSP00000381984.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2022

The c.449A>G (p.N150S) alteration is located in exon 4 (coding exon 4) of the RPRD1A gene. This alteration results from a A to G substitution at nucleotide position 449, causing the asparagine (N) at amino acid position 150 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.024	.;T;T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	.;.;D;D
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.091	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	.;L;L;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.48	.;N;N;.
REVEL	Benign	0.081
Sift	Benign	0.42	.;T;T;.
Sift4G	Benign	0.65	T;T;T;T
Polyphen		0.012	B;B;B;B
Vest4		0.17
MutPred		0.22		.;Gain of phosphorylation at N150 (P = 0.0209);Gain of phosphorylation at N150 (P = 0.0209);.;
MVP		0.40
MPC		0.30
ClinPred		0.64	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.061

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-33610808;