rs149304917

Variant names:

• chr2-9455693-G-A
• rs149304917
• NM_016207.4:c.1539G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-9455693-G-A
• chr2-9455693-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_016207.4(CPSF3):​c.1539G>A​(p.Gln513Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000498 in 1,614,122 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (1 hom.)
• Consequence: CPSF3 NM_016207.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.58
• Publications: 1 publications found

Genes affected

CPSF3 (HGNC:2326): (cleavage and polyadenylation specific factor 3) This gene encodes a member of the metallo-beta-lactamase family. The encoded protein is a 73kDa subunit of the cleavage and polyadenylation specificity factor and functions as an endonuclease that recognizes the pre-mRNA 3'-cleavage site AAUAAA prior to polyadenylation. It also cleaves after the pre-mRNA sequence ACCCA during histone 3'-end pre-mRNA processing. [provided by RefSeq, Oct 2012]

CPSF3 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with microcephaly, hypotonia, nystagmus, and seizures

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 2-9455693-G-A is Benign according to our data. Variant chr2-9455693-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2650664.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.58 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016207.4. 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
	CPSF3	NM_016207.4	MANE Select	c.1539G>A	p.Gln513Gln	synonymous	Exon 13 of 18	NP_057291.1	Q9UKF6
	CPSF3	NM_001321836.2		c.1551G>A	p.Gln517Gln	synonymous	Exon 14 of 19	NP_001308765.1
	CPSF3	NM_001321833.2		c.1428G>A	p.Gln476Gln	synonymous	Exon 13 of 18	NP_001308762.1	G5E9W3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPSF3	ENST00000238112.8	TSL:1 MANE Select	c.1539G>A	p.Gln513Gln	synonymous	Exon 13 of 18	ENSP00000238112.3	Q9UKF6
	CPSF3	ENST00000460593.1	TSL:1	c.1428G>A	p.Gln476Gln	synonymous	Exon 13 of 18	ENSP00000418957.1	G5E9W3
	CPSF3	ENST00000882814.1		c.1623G>A	p.Gln541Gln	synonymous	Exon 14 of 19	ENSP00000552873.1

Frequencies

GnomAD3 genomes AF: 0.00221 AC: 336 AN: 152212 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00758

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000692 AC: 174 AN: 251404 AF XY: 0.000515

Gnomad AFR exome AF: 0.00658

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000149

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000317 AC: 463 AN: 1461792 Hom.: 1 Cov.: 30 AF XY: 0.000308 AC XY: 224 AN XY: 727192

African (AFR) AF: 0.00851 AC: 285 AN: 33474

American (AMR) AF: 0.00123 AC: 55 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00111 AC: 29 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5768

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111958

Other (OTH) AF: 0.000878 AC: 53 AN: 60392

GnomAD4 genome AF: 0.00224 AC: 341 AN: 152330 Hom.: 1 Cov.: 32 AF XY: 0.00203 AC XY: 151 AN XY: 74482

African (AFR) AF: 0.00767 AC: 319 AN: 41574

American (AMR) AF: 0.000850 AC: 13 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

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

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68038

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00132 Hom.: 1

Bravo AF: 0.00246

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	7.3
DANN	Benign	0.73
PhyloP100		3.6
Mutation Taster		=99/1	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: rs149304917; hg19: chr2-9595822;