NM_001326.3:c.1316A>C

Variant names:

• chr11-33096365-T-G
• NM_001326.3:c.1316A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001326.3(CSTF3):​c.1316A>C​(p.Lys439Thr) variant causes a missense change involving the alteration of a 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: CSTF3 NM_001326.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82
• Publications: 0 publications found

Genes affected

CSTF3 (HGNC:2485): (cleavage stimulation factor subunit 3) The protein encoded by this gene is one of three (including CSTF1 and CSTF2) cleavage stimulation factors that combine to form the cleavage stimulation factor complex (CSTF). This complex is involved in the polyadenylation and 3' end cleavage of pre-mRNAs. The encoded protein functions as a homodimer and interacts directly with both CSTF1 and CSTF2 in the CSTF complex. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

TCP11L1 (HGNC:25655): (t-complex 11 like 1) Predicted to be involved in signal transduction. Located in microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001326.3. 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
	CSTF3	NM_001326.3	MANE Select	c.1316A>C	p.Lys439Thr	missense	Exon 15 of 21	NP_001317.1	Q12996-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSTF3	ENST00000323959.9	TSL:1 MANE Select	c.1316A>C	p.Lys439Thr	missense	Exon 15 of 21	ENSP00000315791.4	Q12996-1
	CSTF3	ENST00000524827.6	TSL:3	c.1412A>C	p.Lys471Thr	missense	Exon 16 of 22	ENSP00000431355.2	E9PLP8
	CSTF3	ENST00000954368.1		c.1316A>C	p.Lys439Thr	missense	Exon 15 of 21	ENSP00000624427.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.5	L
PhyloP100		7.8
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.010	D
Polyphen		0.88	P
Vest4		0.78
MutPred		0.62		Loss of ubiquitination at K439 (P = 0.0326)
MVP		0.76
MPC		1.8
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.70
gMVP		0.75
Mutation Taster		=15/85	disease causing

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

hg19: chr11-33117911;