21-45941676-G-T

Variant names:

• chr21-45941676-G-T
• rs61736689
• NM_001384156.1:c.1086G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001384156.1(PCBP3):​c.1086G>T​(p.Thr362Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,606,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T362T) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PCBP3 NM_001384156.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.740
• Publications: 2 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=0.74 with no splicing effect.

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.1086G>T	p.Thr362Thr	synonymous	Exon 18 of 18	NP_001371085.1	P57721-1
	PCBP3	NM_001348240.2		c.1155G>T	p.Thr385Thr	synonymous	Exon 17 of 17	NP_001335169.1
	PCBP3	NM_001382279.1		c.1155G>T	p.Thr385Thr	synonymous	Exon 15 of 15	NP_001369208.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCBP3	ENST00000681687.1	MANE Select	c.1086G>T	p.Thr362Thr	synonymous	Exon 18 of 18	ENSP00000505796.1	P57721-1
	PCBP3	ENST00000400304.1	TSL:1	c.1056G>T	p.Thr352Thr	synonymous	Exon 13 of 13	ENSP00000383159.1	E9PFP8
	PCBP3	ENST00000400308.5	TSL:1	c.1008G>T	p.Thr336Thr	synonymous	Exon 13 of 13	ENSP00000383163.1	P57721-2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152056 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1454414 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 723374

African (AFR) AF: 0.00 AC: 0 AN: 33236

American (AMR) AF: 0.00 AC: 0 AN: 43548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25950

East Asian (EAS) AF: 0.00 AC: 0 AN: 39174

South Asian (SAS) AF: 0.00 AC: 0 AN: 84762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1108570

Other (OTH) AF: 0.00 AC: 0 AN: 60118

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152056 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74254

African (AFR) AF: 0.00 AC: 0 AN: 41378

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	1.9
DANN	Benign	0.70
PhyloP100		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs61736689; hg19: chr21-47361590;