rs440207

Variant names:

• chr21-45914500-C-T
• rs440207
• NM_001384156.1:c.675+475C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001348241.2(PCBP3):​c.667C>T​(p.Arg223*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 216,964 control chromosomes in the GnomAD database, including 24,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.47 (19136 hom., cov: 34)
  • Exomes 𝑓: 0.40 (5323 hom.)
• Consequence: PCBP3 NM_001348241.2 stop_gained
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0700
• Publications: 3 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]

ENSG00000280604 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP6: Variant 21-45914500-C-T is Benign according to our data. Variant chr21-45914500-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060839.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348241.2. 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.675+475C>T		intron	N/A	NP_001371085.1	P57721-1
	PCBP3	NM_001348241.2		c.667C>T	p.Arg223*	stop_gained	Exon 12 of 18	NP_001335170.1
	PCBP3	NM_001348240.2		c.744+406C>T		intron	N/A	NP_001335169.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCBP3	ENST00000681687.1	MANE Select	c.675+475C>T		intron	N/A	ENSP00000505796.1	P57721-1
	PCBP3	ENST00000400304.1	TSL:1	c.648+406C>T		intron	N/A	ENSP00000383159.1	E9PFP8
	PCBP3	ENST00000400308.5	TSL:1	c.601-3088C>T		intron	N/A	ENSP00000383163.1	P57721-2

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71916 AN: 152050 Hom.: 19105 Cov.: 34

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.396 AC: 25627 AN: 64796 Hom.: 5323 Cov.: 0 AF XY: 0.394 AC XY: 12693 AN XY: 32184

African (AFR) AF: 0.731 AC: 1701 AN: 2328

American (AMR) AF: 0.346 AC: 652 AN: 1884

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1078 AN: 2622

East Asian (EAS) AF: 0.395 AC: 1709 AN: 4322

South Asian (SAS) AF: 0.362 AC: 856 AN: 2366

European-Finnish (FIN) AF: 0.342 AC: 1183 AN: 3456

Middle Eastern (MID) AF: 0.449 AC: 150 AN: 334

European-Non Finnish (NFE) AF: 0.382 AC: 16442 AN: 43032

Other (OTH) AF: 0.417 AC: 1856 AN: 4452

GnomAD4 genome AF: 0.473 AC: 71985 AN: 152168 Hom.: 19136 Cov.: 34 AF XY: 0.467 AC XY: 34713 AN XY: 74396

African (AFR) AF: 0.728 AC: 30265 AN: 41554

American (AMR) AF: 0.393 AC: 6007 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1424 AN: 3468

East Asian (EAS) AF: 0.325 AC: 1677 AN: 5160

South Asian (SAS) AF: 0.379 AC: 1828 AN: 4826

European-Finnish (FIN) AF: 0.327 AC: 3459 AN: 10586

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25897 AN: 67958

Other (OTH) AF: 0.441 AC: 932 AN: 2114

Alfa AF: 0.433 Hom.: 2094

Bravo AF: 0.491

Asia WGS AF: 0.377 AC: 1315 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PCBP3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.67
PhyloP100		0.070
Mutation Taster		=100/0	polymorphism (auto)

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: rs440207; hg19: chr21-47334414; COSMIC: COSV68407218;