Variant chr14-72674300-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001280542.3(DPF3):c.811A>T(p.Met271Leu) 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 1,460,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DPF3
NM_001280542.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.68

Variant links:

Genes affected

DPF3 (HGNC:17427): (double PHD fingers 3) This gene encodes a member of the D4 protein family. The encoded protein is a transcription regulator that binds acetylated histones and is a component of the BAF chromatin remodeling complex. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

DPF3 links:

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ACMG classification

Classification made for transcript

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=0.14067891).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DPF3	NM_001280542.3 linkuse as main transcript	c.811A>T	p.Met271Leu	missense_variant	8/11	ENST00000556509.6
DPF3	NM_001280544.2 linkuse as main transcript	c.976A>T	p.Met326Leu	missense_variant	8/10
DPF3	NM_001280543.2 linkuse as main transcript	c.841A>T	p.Met281Leu	missense_variant	9/11
DPF3	NM_012074.5 linkuse as main transcript	c.811A>T	p.Met271Leu	missense_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPF3	ENST00000556509.6 linkuse as main transcript	c.811A>T	p.Met271Leu	missense_variant	8/11	1	NM_001280542.3	P1	Q92784-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460740

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726508

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2023

The c.811A>T (p.M271L) alteration is located in exon 8 (coding exon 8) of the DPF3 gene. This alteration results from a A to T substitution at nucleotide position 811, causing the methionine (M) at amino acid position 271 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Benign

0.0011

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.020

T;T;.;.;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.053

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.79

T;T;T;T;.

M_CAP

Benign

0.074

MetaRNN

Benign

0.14

T;T;T;T;T

MetaSVM

Benign

-0.36

MutationAssessor

Benign

-1.1

N;.;N;.;.

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.80

N;.;N;.;N

REVEL

Benign

0.15

Sift

Benign

0.43

T;.;T;.;T

Sift4G

Benign

0.28

T;T;T;T;T

Polyphen

0.0

B;.;B;.;.

Vest4

0.29

MutPred

0.34

Gain of ubiquitination at K274 (P = 0.1093);.;Gain of ubiquitination at K274 (P = 0.1093);.;.;

MVP

0.26

MPC

0.37

ClinPred

0.32

GERP RS

5.5

Varity_R

0.25

gMVP

0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over