chr21-45917570-G-GTC

Variant names:

• chr21-45917570-G-GTC
• rs548673780
• NM_001384156.1:c.676-4_676-3dupCT

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_001384156.1(PCBP3):​c.676-4_676-3dupCT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,549,920 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: PCBP3 NM_001384156.1 splice_acceptor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.03763441 fraction of the gene. Cryptic splice site detected, with MaxEntScore 15, offset of 0 (no position change), new splice context is: gtctctctctctctctctAGgcc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCBP3	NM_001384156.1	c.676-4_676-3dupCT		splice_acceptor_variant, intron_variant	Intron 12 of 17	ENST00000681687.1	NP_001371085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCBP3	ENST00000681687.1	c.676-18_676-17insTC		intron_variant	Intron 12 of 17		NM_001384156.1	ENSP00000505796.1

Frequencies

GnomAD3 genomes AF: 0.0000793 AC: 12 AN: 151294 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.000480

GnomAD4 exome AF: 0.000208 AC: 291 AN: 1398626 Hom.: 1 Cov.: 28 AF XY: 0.000197 AC XY: 137 AN XY: 695088

Gnomad4 AFR exome AF: 0.0000313

Gnomad4 AMR exome AF: 0.0000476

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000184

Gnomad4 SAS exome AF: 0.000136

Gnomad4 FIN exome AF: 0.0000392

Gnomad4 NFE exome AF: 0.000241

Gnomad4 OTH exome AF: 0.000173

GnomAD4 genome AF: 0.0000793 AC: 12 AN: 151294 Hom.: 0 Cov.: 31 AF XY: 0.0000812 AC XY: 6 AN XY: 73852

Gnomad4 AFR AF: 0.0000485

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000133

Gnomad4 OTH AF: 0.000480

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs548673780; hg19: chr21-47337484;