20-38048372-A-T

Position:

• chr20-38048372-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021215.4(RPRD1B):​c.306A>T​(p.Lys102Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPRD1B NM_021215.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.06

Genes affected

RPRD1B (HGNC:16209): (regulation of nuclear pre-mRNA domain containing 1B) Enables RNA polymerase II complex binding activity and identical protein binding activity. Involved in positive regulation of cell population proliferation; regulation of cell cycle process; and regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of RNA polymerase II, holoenzyme. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3380546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPRD1B	NM_021215.4	c.306A>T	p.Lys102Asn	missense_variant	3/7	ENST00000373433.9	NP_067038.1
RPRD1B	XM_047440347.1	c.-231A>T		5_prime_UTR_variant	1/5		XP_047296303.1
RPRD1B	XM_047440346.1	c.91+7808A>T		intron_variant			XP_047296302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPRD1B	ENST00000373433.9	c.306A>T	p.Lys102Asn	missense_variant	3/7	1	NM_021215.4	ENSP00000362532	P1
RPRD1B	ENST00000462548.6	c.176A>T	p.Asn59Ile	missense_variant, NMD_transcript_variant	2/6	5		ENSP00000436816
RPRD1B	ENST00000495457.1	c.281+7808A>T		intron_variant, NMD_transcript_variant		4		ENSP00000433947

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 25, 2022

The c.306A>T (p.K102N) alteration is located in exon 3 (coding exon 3) of the RPRD1B gene. This alteration results from a A to T substitution at nucleotide position 306, causing the lysine (K) at amino acid position 102 to be replaced by an asparagine (N). 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	Pathogenic	0.82
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.17
Sift	Benign	0.081	T
Sift4G	Benign	0.22	T
Polyphen		0.93	P
Vest4		0.41
MutPred		0.52		Loss of ubiquitination at K102 (P = 0.021);
MVP		0.16
MPC		1.3
ClinPred		0.78	D
GERP RS		4.7
Varity_R		0.63
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr20-36676774;