Variant 19-4409695-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005483.3(CHAF1A):c.896C>T(p.Pro299Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

CHAF1A
NM_005483.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.479

Variant links:

Genes affected

CHAF1A (HGNC:1910): (chromatin assembly factor 1 subunit A) Chromatin assembly factor I (CAF1) is a nuclear complex consisting of p50, p60 (CHAF1B; MIM 601245), and p150 (CHAF1A) subunits that assembles histone octamers onto replicating DNA in vitro (Kaufman et al., 1995 [PubMed 7600578]).[supplied by OMIM, Mar 2008]

CHAF1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03619525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHAF1A	NM_005483.3 linkuse as main transcript	c.896C>T	p.Pro299Leu	missense_variant	3/15	ENST00000301280.10	NP_005474.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHAF1A	ENST00000301280.10 linkuse as main transcript	c.896C>T	p.Pro299Leu	missense_variant	3/15	1	NM_005483.3	ENSP00000301280	P1	Q13111-1
CHAF1A	ENST00000587739.1 linkuse as main transcript	c.251C>T	p.Pro84Leu	missense_variant	1/5	5		ENSP00000467296

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000401

AC:

AN:

249070

Hom.:

AF XY:

0.0000519

AC XY:

AN XY:

134836

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000628

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000369

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000432

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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.896C>T (p.P299L) alteration is located in exon 3 (coding exon 3) of the CHAF1A gene. This alteration results from a C to T substitution at nucleotide position 896, causing the proline (P) at amino acid position 299 to be replaced by a leucine (L). 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

0.057

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.37

DANN

Benign

0.64

DEOGEN2

Benign

0.043

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.97

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.058

Sift

Benign

0.41

T;.

Sift4G

Benign

0.39

T;T

Polyphen

0.0040

B;.

Vest4

0.13

MutPred

0.19

Loss of glycosylation at P299 (P = 0.0104);.;

MVP

0.31

MPC

0.14

ClinPred

0.014

GERP RS

-12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.019

gMVP

0.045

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