chr21-45896212-C-T

Variant names:

• chr21-45896212-C-T
• rs113211675
• NM_001384156.1:c.15C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001348242.2(PCBP3):​c.-82C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,551,550 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (11 hom., cov: 34)
  • Exomes 𝑓: 0.00087 (6 hom.)
• Consequence: PCBP3 NM_001348242.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.08
• Publications: 1 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: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 21-45896212-C-T is Benign according to our data. Variant chr21-45896212-C-T is described in ClinVar as Benign. ClinVar VariationId is 712872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0057 (868/152398) while in subpopulation AFR AF = 0.0185 (770/41600). AF 95% confidence interval is 0.0174. There are 11 homozygotes in GnomAd4. There are 419 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348242.2. 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.15C>T	p.Asp5Asp	synonymous	Exon 6 of 18	NP_001371085.1	P57721-1
	PCBP3	NM_001348242.2		c.-82C>T		5_prime_UTR_premature_start_codon_gain	Exon 7 of 19	NP_001335171.1
	PCBP3	NM_001382276.1		c.-82C>T		5_prime_UTR_premature_start_codon_gain	Exon 7 of 19	NP_001369205.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCBP3	ENST00000681687.1	MANE Select	c.15C>T	p.Asp5Asp	synonymous	Exon 6 of 18	ENSP00000505796.1	P57721-1
	PCBP3	ENST00000400308.5	TSL:1	c.15C>T	p.Asp5Asp	synonymous	Exon 2 of 13	ENSP00000383163.1	P57721-2
	PCBP3	ENST00000449640.5	TSL:5	c.-82C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 14	ENSP00000401198.2	E9PFP8

Frequencies

GnomAD3 genomes AF: 0.00567 AC: 863 AN: 152280 Hom.: 11 Cov.: 34

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00955

GnomAD2 exomes AF: 0.00174 AC: 275 AN: 158454 AF XY: 0.00148

Gnomad AFR exome AF: 0.0217

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00586

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000210

Gnomad OTH exome AF: 0.000446

GnomAD4 exome AF: 0.000866 AC: 1211 AN: 1399152 Hom.: 6 Cov.: 32 AF XY: 0.000809 AC XY: 558 AN XY: 690092

African (AFR) AF: 0.0214 AC: 676 AN: 31578

American (AMR) AF: 0.00120 AC: 43 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00489 AC: 123 AN: 25178

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35736

South Asian (SAS) AF: 0.000139 AC: 11 AN: 79196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49520

Middle Eastern (MID) AF: 0.00154 AC: 8 AN: 5210

European-Non Finnish (NFE) AF: 0.000199 AC: 215 AN: 1078950

Other (OTH) AF: 0.00231 AC: 134 AN: 58080

GnomAD4 genome AF: 0.00570 AC: 868 AN: 152398 Hom.: 11 Cov.: 34 AF XY: 0.00562 AC XY: 419 AN XY: 74524

African (AFR) AF: 0.0185 AC: 770 AN: 41600

American (AMR) AF: 0.00242 AC: 37 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68042

Other (OTH) AF: 0.00945 AC: 20 AN: 2116

Alfa AF: 0.00297 Hom.: 1

Bravo AF: 0.00674

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	PCBP3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Benign	0.71
PhyloP100		2.1
PromoterAI		-0.010	Neutral
Mutation Taster		=100/0	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: rs113211675; hg19: chr21-47316126;