rs61736689

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr21-45941676-G-A
• chr21-45941676-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001384156.1(PCBP3):​c.1086G>A​(p.Thr362Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,606,558 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (73 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (49 hom.)
• Consequence: PCBP3 NM_001384156.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BP6: Variant 21-45941676-G-A is Benign according to our data. Variant chr21-45941676-G-A is described in ClinVar as Benign. ClinVar VariationId is 781522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.74 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0538 is higher than 0.05.

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>A	p.Thr362Thr	synonymous	Exon 18 of 18	NP_001371085.1	P57721-1
	PCBP3	NM_001348240.2		c.1155G>A	p.Thr385Thr	synonymous	Exon 17 of 17	NP_001335169.1
	PCBP3	NM_001382279.1		c.1155G>A	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>A	p.Thr362Thr	synonymous	Exon 18 of 18	ENSP00000505796.1	P57721-1
	PCBP3	ENST00000400304.1	TSL:1	c.1056G>A	p.Thr352Thr	synonymous	Exon 13 of 13	ENSP00000383159.1	E9PFP8
	PCBP3	ENST00000400308.5	TSL:1	c.1008G>A	p.Thr336Thr	synonymous	Exon 13 of 13	ENSP00000383163.1	P57721-2

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2443 AN: 152052 Hom.: 72 Cov.: 33

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00417 AC: 1008 AN: 241590 AF XY: 0.00300

Gnomad AFR exome AF: 0.0552

Gnomad AMR exome AF: 0.00413

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000931

Gnomad NFE exome AF: 0.000181

Gnomad OTH exome AF: 0.00156

GnomAD4 exome AF: 0.00163 AC: 2375 AN: 1454388 Hom.: 49 Cov.: 30 AF XY: 0.00140 AC XY: 1016 AN XY: 723370

African (AFR) AF: 0.0538 AC: 1788 AN: 33214

American (AMR) AF: 0.00452 AC: 197 AN: 43544

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 25950

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

South Asian (SAS) AF: 0.000106 AC: 9 AN: 84762

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53314

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5742

European-Non Finnish (NFE) AF: 0.000124 AC: 137 AN: 1108570

Other (OTH) AF: 0.00379 AC: 228 AN: 60118

GnomAD4 genome AF: 0.0161 AC: 2446 AN: 152170 Hom.: 73 Cov.: 33 AF XY: 0.0157 AC XY: 1165 AN XY: 74382

African (AFR) AF: 0.0557 AC: 2310 AN: 41496

American (AMR) AF: 0.00660 AC: 101 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

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

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

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67992

Other (OTH) AF: 0.0109 AC: 23 AN: 2108

Alfa AF: 0.00283 Hom.: 5

Bravo AF: 0.0184

Asia WGS AF: 0.00289 AC: 10 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	-0.22
CADD	Benign	6.5
DANN	Benign	0.71
PhyloP100		0.74
Mutation Taster		=100/0	polymorphism

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; COSMIC: COSV68408285; COSMIC: COSV68408285;