19-4409043-G-T

Position:

• chr19-4409043-G-T

Variant summary

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

The NM_005483.3(CHAF1A):​c.244G>T​(p.Gly82Cys) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CHAF1A NM_005483.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82

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=0.2554557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHAF1A	NM_005483.3	c.244G>T	p.Gly82Cys	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.244G>T	p.Gly82Cys	missense_variant	3/15	1	NM_005483.3	ENSP00000301280.4
CHAF1A	ENST00000585854.1	c.193G>T	p.Gly65Cys	missense_variant	2/2	2		ENSP00000465142.1
CHAF1A	ENST00000587580.1	n.330G>T		non_coding_transcript_exon_variant	3/3	3

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

Oct 30, 2024

The c.244G>T (p.G82C) alteration is located in exon 3 (coding exon 3) of the CHAF1A gene. This alteration results from a G to T substitution at nucleotide position 244, causing the glycine (G) at amino acid position 82 to be replaced by a cysteine (C). 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	0.10
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.049	T;.
Eigen	Benign	-0.011
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.74	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.2	N;.
REVEL	Benign	0.13
Sift	Uncertain	0.0090	D;.
Sift4G	Uncertain	0.015	D;D
Polyphen		0.98	D;.
Vest4		0.36
MutPred		0.28		Gain of sheet (P = 0.0477);.;
MVP		0.56
MPC		0.62
ClinPred		0.56	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.21

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: chr19-4409040;