Variant 20-56399181-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001324.3(CSTF1):c.860A>G(p.Lys287Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CSTF1
NM_001324.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.83

Variant links:

Genes affected

CSTF1 (HGNC:2483): (cleavage stimulation factor subunit 1) This gene encodes one of three subunits which combine to form cleavage stimulation factor (CSTF). CSTF is involved in the polyadenylation and 3'end cleavage of pre-mRNAs. Similar to mammalian G protein beta subunits, this protein contains transducin-like repeats. Several transcript variants with different 5' UTR, but encoding the same protein, have been found for this gene. [provided by RefSeq, Jul 2008]

CSTF1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.796

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSTF1	NM_001324.3 linkuse as main transcript	c.860A>G	p.Lys287Arg	missense_variant	5/6	ENST00000217109.9	NP_001315.1	Q05048
CSTF1	NM_001033521.2 linkuse as main transcript	c.860A>G	p.Lys287Arg	missense_variant	5/6		NP_001028693.1	Q05048
CSTF1	NM_001033522.2 linkuse as main transcript	c.860A>G	p.Lys287Arg	missense_variant	5/6		NP_001028694.1	Q05048
CSTF1	XM_011528600.2 linkuse as main transcript	c.860A>G	p.Lys287Arg	missense_variant	5/6		XP_011526902.1	Q05048

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSTF1	ENST00000217109.9 linkuse as main transcript	c.860A>G	p.Lys287Arg	missense_variant	5/6	1	NM_001324.3	ENSP00000217109.4		Q05048

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.860A>G (p.K287R) alteration is located in exon 5 (coding exon 4) of the CSTF1 gene. This alteration results from a A to G substitution at nucleotide position 860, causing the lysine (K) at amino acid position 287 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T;T

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;D;D

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.6

.;L;.

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Uncertain

0.42

Sift

Pathogenic

0.0

D;D;D

Sift4G

Benign

0.13

T;T;T

Polyphen

1.0

.;D;.

Vest4

0.83

MutPred

0.57

Loss of methylation at K287 (P = 0.0301);Loss of methylation at K287 (P = 0.0301);Loss of methylation at K287 (P = 0.0301);

MVP

0.85

MPC

2.1

ClinPred

0.97

GERP RS

5.6

Varity_R

0.84

gMVP

0.51

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over