chr19-4409128-T-C

Variant names:

• chr19-4409128-T-C
• NM_005483.3:c.329T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005483.3(CHAF1A):​c.329T>C​(p.Ile110Thr) 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. 17/22 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: -0.163
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0503394).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005483.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHAF1A	NM_005483.3	MANE Select	c.329T>C	p.Ile110Thr	missense	Exon 3 of 15	NP_005474.2	Q13111-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHAF1A	ENST00000301280.10	TSL:1 MANE Select	c.329T>C	p.Ile110Thr	missense	Exon 3 of 15	ENSP00000301280.4	Q13111-1
	CHAF1A	ENST00000900275.1		c.329T>C	p.Ile110Thr	missense	Exon 3 of 17	ENSP00000570334.1
	CHAF1A	ENST00000926550.1		c.329T>C	p.Ile110Thr	missense	Exon 3 of 17	ENSP00000596609.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.8
DANN	Benign	0.70
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.16
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.058
Sift	Benign	0.85	T
Sift4G	Benign	0.51	T
Polyphen		0.0040	B
Vest4		0.046
MutPred		0.32		Gain of disorder (P = 0.0216)
MVP		0.44
MPC		0.23
ClinPred		0.064	T
GERP RS		3.1
PromoterAI		-0.0032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.047
gMVP		0.045
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

hg19: chr19-4409125;