1-3865815-T-G

Variant names:

• chr1-3865815-T-G
• rs938964317
• NM_004402.4:c.245T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004402.4(DFFB):​c.245T>G​(p.Val82Gly) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V82E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DFFB NM_004402.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 0 publications found

Genes affected

DFFB (HGNC:2773): (DNA fragmentation factor subunit beta) Apoptosis is a cell death process that removes toxic and/or useless cells during mammalian development. The apoptotic process is accompanied by shrinkage and fragmentation of the cells and nuclei and degradation of the chromosomal DNA into nucleosomal units. DNA fragmentation factor (DFF) is a heterodimeric protein of 40-kD (DFFB) and 45-kD (DFFA) subunits. DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis. DFF becomes activated when DFFA is cleaved by caspase-3. The cleaved fragments of DFFA dissociate from DFFB, the active component of DFF. DFFB has been found to trigger both DNA fragmentation and chromatin condensation during apoptosis. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene but the biological validity of some of these variants has not been determined. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39947444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DFFB	NM_004402.4	c.245T>G	p.Val82Gly	missense_variant	Exon 3 of 7	ENST00000378209.8	NP_004393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DFFB	ENST00000378209.8	c.245T>G	p.Val82Gly	missense_variant	Exon 3 of 7	1	NM_004402.4	ENSP00000367454.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Benign	0.78
DEOGEN2	Benign	0.11	T;D
Eigen	Benign	-0.040
Eigen_PC	Benign	-0.071
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.22	T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	.;M
PhyloP100		1.9
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.7	.;D
REVEL	Benign	0.13
Sift	Uncertain	0.0010	.;D
Sift4G	Benign	0.30	T;D
Polyphen		0.73	P;P
Vest4		0.42
MutPred		0.50		.;Gain of loop (P = 0.0435);
MVP		0.69
MPC		0.30
ClinPred		0.83	D
GERP RS		3.3
Varity_R		0.47
gMVP		0.73
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

dbSNP: rs938964317; hg19: chr1-3782379;