19-4409428-T-C

Position:

• chr19-4409428-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005483.3(CHAF1A):​c.629T>C​(p.Leu210Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CHAF1A NM_005483.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.593

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13442689).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHAF1A	NM_005483.3	c.629T>C	p.Leu210Pro	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	c.629T>C	p.Leu210Pro	missense_variant	3/15	1	NM_005483.3	ENSP00000301280.4
CHAF1A	ENST00000587739.1	c.-17T>C		upstream_gene_variant		5		ENSP00000467296.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

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, 2024

The c.629T>C (p.L210P) alteration is located in exon 3 (coding exon 3) of the CHAF1A gene. This alteration results from a T to C substitution at nucleotide position 629, causing the leucine (L) at amino acid position 210 to be replaced by a proline (P). 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	0.073
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	11
DANN	Benign	0.94
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	0.96	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.48	P
Vest4		0.20
MutPred		0.24		Loss of stability (P = 0.0203);
MVP		0.42
MPC		0.23
ClinPred		0.17	T
GERP RS		3.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.2
Varity_R		0.18
gMVP		0.37

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: chr19-4409425;