Variant 19-14120638-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018154.3(ASF1B):c.430C>T(p.Pro144Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/20 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ASF1B
NM_018154.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.76

Variant links:

Genes affected

ASF1B (HGNC:20996): (anti-silencing function 1B histone chaperone) This gene encodes a member of the H3/H4 family of histone chaperone proteins and is similar to the anti-silencing function-1 gene in yeast. The encoded protein is the substrate of the tousled-like kinase family of cell cycle-regulated kinases, and may play a key role in modulating the nucleosome structure of chromatin by ensuring a constant supply of histones at sites of nucleosome assembly. [provided by RefSeq, Jul 2008]

ASF1B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.923

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASF1B	NM_018154.3 linkuse as main transcript	c.430C>T	p.Pro144Ser	missense_variant	4/4	ENST00000263382.8	NP_060624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ASF1B	ENST00000263382.8 linkuse as main transcript	c.430C>T	p.Pro144Ser	missense_variant	4/4	1	NM_018154.3	ENSP00000263382	P1
ASF1B	ENST00000592798.5 linkuse as main transcript	c.253C>T	p.Pro85Ser	missense_variant	3/3	2		ENSP00000468513
ASF1B	ENST00000589468.1 linkuse as main transcript	c.*167C>T		3_prime_UTR_variant, NMD_transcript_variant	3/3	3		ENSP00000466409
ASF1B	ENST00000590835.5 linkuse as main transcript	c.*153C>T		3_prime_UTR_variant, NMD_transcript_variant	4/4	5		ENSP00000464802

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251242

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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

Aug 08, 2022

The c.430C>T (p.P144S) alteration is located in exon 4 (coding exon 4) of the ASF1B gene. This alteration results from a C to T substitution at nucleotide position 430, causing the proline (P) at amino acid position 144 to be replaced by a serine (S). 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

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.44

BayesDel_noAF

Pathogenic

0.47

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.59

D;.

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

1.0

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

1.0

D;D

M_CAP

Benign

0.077

MetaRNN

Pathogenic

0.92

D;D

MetaSVM

Uncertain

0.50

MutationAssessor

Pathogenic

3.4

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-7.5

D;.

REVEL

Pathogenic

0.94

Sift

Uncertain

0.0010

D;.

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;.

Vest4

0.82

MutPred

0.84

Loss of stability (P = 0.03);.;

MVP

0.65

MPC

0.80

ClinPred

1.0

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.90

gMVP

0.81

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over