19-4409411-A-ACGGAGCTGCC

Variant names:

• chr19-4409411-A-ACGGAGCTGCC
• NM_005483.3:c.621_630dupCCCGGAGCTG

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_005483.3(CHAF1A):​c.621_630dupCCCGGAGCTG​(p.Thr211ProfsTer20) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CHAF1A NM_005483.3 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.865

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-4409411-A-ACGGAGCTGCC is Pathogenic according to our data. Variant chr19-4409411-A-ACGGAGCTGCC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3242439.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHAF1A	NM_005483.3	c.621_630dupCCCGGAGCTG	p.Thr211ProfsTer20	frameshift_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.621_630dupCCCGGAGCTG	p.Thr211ProfsTer20	frameshift_variant	Exon 3 of 15	1	NM_005483.3	ENSP00000301280.4
CHAF1A	ENST00000587739.1	c.-34_-33insCGGAGCTGCC		upstream_gene_variant		5		ENSP00000467296.1
CHAF1A	ENST00000585854.1	c.*108_*109insCGGAGCTGCC		downstream_gene_variant		2		ENSP00000465142.1
CHAF1A	ENST00000587580.1	n.*204_*205insCGGAGCTGCC		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Craniofacial microsomia Pathogenic:1

Apr 01, 2024

Molecular Genetics laboratory, Necker Hospital

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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: chr19-4409408;