rs754501034

Variant names:

• chr19-4409422-C-A
• NM_005483.3:c.623C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-4409422-C-A
• chr19-4409422-C-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.623C>A​(p.Pro208Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CHAF1A NM_005483.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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]

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=0.08955103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHAF1A	NM_005483.3	c.623C>A	p.Pro208Gln	missense_variant	Exon 3 of 15	ENST00000301280.10	NP_005474.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHAF1A	ENST00000301280.10	c.623C>A	p.Pro208Gln	missense_variant	Exon 3 of 15	1	NM_005483.3	ENSP00000301280.4
CHAF1A	ENST00000587739.1	c.-23C>A		upstream_gene_variant		5		ENSP00000467296.1
CHAF1A	ENST00000585854.1	c.*119C>A		downstream_gene_variant		2		ENSP00000465142.1
CHAF1A	ENST00000587580.1	n.*215C>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461876 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.3
DANN	Benign	0.90
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.11
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.23	T
Polyphen		0.53	P
Vest4		0.15
MutPred		0.14		Loss of glycosylation at T211 (P = 0.0829);
MVP		0.36
MPC		0.13
ClinPred		0.17	T
GERP RS		3.3
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		3.3
Varity_R		0.023
gMVP		0.14

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: chr19-4409419;