2-9443619-G-C

Variant names:

• chr2-9443619-G-C
• NM_016207.4:c.1200G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016207.4(CPSF3):​c.1200G>C​(p.Gln400His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPSF3 NM_016207.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.18

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPSF3	NM_016207.4	c.1200G>C	p.Gln400His	missense_variant	Exon 10 of 18	ENST00000238112.8	NP_057291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPSF3	ENST00000238112.8	c.1200G>C	p.Gln400His	missense_variant	Exon 10 of 18	1	NM_016207.4	ENSP00000238112.3
CPSF3	ENST00000460593.1	c.1089G>C	p.Gln363His	missense_variant	Exon 10 of 18	1		ENSP00000418957.1
CPSF3	ENST00000489629.1	n.352G>C		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Nov 30, 2021

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.56
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.090
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.85	L;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.15
Sift	Benign	0.12	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.0080	B;.
Vest4		0.64
MutPred		0.39		Gain of disorder (P = 0.2255);.;
MVP		0.56
MPC		1.1
ClinPred		0.56	D
GERP RS		1.3
Varity_R		0.32
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-9583748;