19-14120608-C-T

Position:

• chr19-14120608-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018154.3(ASF1B):​c.460G>A​(p.Asp154Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ASF1B NM_018154.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.72

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38143608).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASF1B	NM_018154.3	c.460G>A	p.Asp154Asn	missense_variant	4/4	ENST00000263382.8	NP_060624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASF1B	ENST00000263382.8	c.460G>A	p.Asp154Asn	missense_variant	4/4	1	NM_018154.3	ENSP00000263382	P1
ASF1B	ENST00000592798.5	c.283G>A	p.Asp95Asn	missense_variant	3/3	2		ENSP00000468513
ASF1B	ENST00000589468.1	c.*197G>A		3_prime_UTR_variant, NMD_transcript_variant	3/3	3		ENSP00000466409
ASF1B	ENST00000590835.5	c.*183G>A		3_prime_UTR_variant, NMD_transcript_variant	4/4	5		ENSP00000464802

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.460G>A (p.D154N) alteration is located in exon 4 (coding exon 4) of the ASF1B gene. This alteration results from a G to A substitution at nucleotide position 460, causing the aspartic acid (D) at amino acid position 154 to be replaced by an asparagine (N). 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	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.7	D;.
REVEL	Uncertain	0.30
Sift	Benign	0.041	D;.
Sift4G	Benign	0.10	T;D
Polyphen		0.61	P;.
Vest4		0.23
MutPred		0.69		Loss of catalytic residue at D154 (P = 0.0205);.;
MVP		0.49
MPC		0.30
ClinPred		0.98	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.46
gMVP		0.59

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.

Other links and lift over

hg19: chr19-14231420;