NM_001384156.1:c.998C>T

Variant names:

• chr21-45940118-C-T
• rs375465014
• NM_001384156.1:c.998C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001384156.1(PCBP3):​c.998C>T​(p.Thr333Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000756 in 1,614,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000068 (0 hom.)
• Consequence: PCBP3 NM_001384156.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.63
• Publications: 7 publications found

Genes affected

PCBP3 (HGNC:8651): (poly(rC) binding protein 3) This gene encodes a member of the KH-domain protein subfamily. Proteins of this subfamily, also referred to as alpha-CPs, bind to RNA with a specificity for C-rich pyrimidine regions. Alpha-CPs play important roles in post-transcriptional activities and have different cellular distributions. The protein encoded by this gene lacks the nuclear localization signals found in other subfamily members. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.029444158).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384156.1. 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
	PCBP3	NM_001384156.1	MANE Select	c.998C>T	p.Thr333Met	missense	Exon 17 of 18	NP_001371085.1	P57721-1
	PCBP3	NM_001348240.2		c.1067C>T	p.Thr356Met	missense	Exon 16 of 17	NP_001335169.1
	PCBP3	NM_001382279.1		c.1067C>T	p.Thr356Met	missense	Exon 14 of 15	NP_001369208.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCBP3	ENST00000681687.1	MANE Select	c.998C>T	p.Thr333Met	missense	Exon 17 of 18	ENSP00000505796.1	P57721-1
	PCBP3	ENST00000400304.1	TSL:1	c.968C>T	p.Thr323Met	missense	Exon 12 of 13	ENSP00000383159.1	E9PFP8
	PCBP3	ENST00000400308.5	TSL:1	c.920C>T	p.Thr307Met	missense	Exon 12 of 13	ENSP00000383163.1	P57721-2

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152244 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000313

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000100 AC: 25 AN: 249510 AF XY: 0.0000739

Gnomad AFR exome AF: 0.000387

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000618

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.0000677 AC: 99 AN: 1461786 Hom.: 0 Cov.: 31 AF XY: 0.0000701 AC XY: 51 AN XY: 727208

African (AFR) AF: 0.000657 AC: 22 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000487 AC: 42 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000288 AC: 32 AN: 1111944

Other (OTH) AF: 0.0000331 AC: 2 AN: 60388

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152362 Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16 AN XY: 74510

African (AFR) AF: 0.000313 AC: 13 AN: 41596

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000164 Hom.: 0

Bravo AF: 0.000106

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000118 AC: 1

ExAC AF: 0.0000990 AC: 12

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

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	Benign	0.062
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.72	N
PhyloP100		4.6
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.036
Sift	Benign	0.11	T
Sift4G	Benign	0.14	T
Polyphen		0.060	B
Vest4		0.24
MVP		0.12
MPC		0.48
ClinPred		0.048	T
GERP RS		2.4
Varity_R		0.044
gMVP		0.85
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs375465014; hg19: chr21-47360032; COSMIC: COSV68409859;