18-36027283-C-A

Position:

• chr18-36027283-C-A

Variant summary

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

The NM_018170.5(RPRD1A):​c.514G>T​(p.Asp172Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPRD1A NM_018170.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84

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]

RPRD1A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPRD1A	NM_018170.5	c.514G>T	p.Asp172Tyr	missense_variant	5/7	ENST00000399022.9	NP_060640.2
RPRD1A	NM_001303413.2	c.514G>T	p.Asp172Tyr	missense_variant	5/7		NP_001290342.1
RPRD1A	NM_001303411.2	c.406G>T	p.Asp136Tyr	missense_variant	6/8		NP_001290340.1
RPRD1A	NM_001303412.2	c.406G>T	p.Asp136Tyr	missense_variant	6/9		NP_001290341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPRD1A	ENST00000399022.9	c.514G>T	p.Asp172Tyr	missense_variant	5/7	1	NM_018170.5	ENSP00000381984.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Mar 07, 2024

The c.514G>T (p.D172Y) alteration is located in exon 5 (coding exon 5) of the RPRD1A gene. This alteration results from a G to T substitution at nucleotide position 514, causing the aspartic acid (D) at amino acid position 172 to be replaced by a tyrosine (Y). 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	Uncertain	0.52
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	.;T;T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	.;.;D;D
M_CAP	Benign	0.0084	T
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.3	.;L;L;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.6	.;D;D;.
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	.;D;D;.
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		0.99	D;P;P;D
Vest4		0.50
MutPred		0.59		.;Loss of disorder (P = 0.0055);Loss of disorder (P = 0.0055);.;
MVP		0.61
MPC		1.1
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.88
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr18-33607246;