chr20-38048372-A-T

Variant names:

• chr20-38048372-A-T
• NM_021215.4:c.306A>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021215.4. 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
	RPRD1B	NM_021215.4	MANE Select	c.306A>T	p.Lys102Asn	missense	Exon 3 of 7	NP_067038.1	Q9NQG5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPRD1B	ENST00000373433.9	TSL:1 MANE Select	c.306A>T	p.Lys102Asn	missense	Exon 3 of 7	ENSP00000362532.4	Q9NQG5
	RPRD1B	ENST00000881436.1		c.306A>T	p.Lys102Asn	missense	Exon 3 of 8	ENSP00000551495.1
	RPRD1B	ENST00000881433.1		c.306A>T	p.Lys102Asn	missense	Exon 3 of 7	ENSP00000551492.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		4.1
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
Mutation Taster		=36/64	disease causing

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

Other links and lift over

hg19: chr20-36676774;