Variant chr7-10982491-G-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_001007157.2(PHF14):c.232G>A(p.Glu78Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000702 in 1,425,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 7.0e-7 ( 0 hom. )

Consequence

PHF14
NM_001007157.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.74

Variant links:

Genes affected

PHF14 (HGNC:22203): (PHD finger protein 14) Predicted to enable histone binding activity. Predicted to be involved in histone H3-K14 acetylation and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including lung alveolus development; negative regulation of mesenchymal cell proliferation involved in lung development; and negative regulation of platelet-derived growth factor receptor-alpha signaling pathway. Predicted to be located in nucleus. Predicted to be part of MOZ/MORF histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

PHF14 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=0.12923625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF14	NM_001007157.2 link	c.232G>A	p.Glu78Lys	missense_variant	3/18	ENST00000634607.2	NP_001007158.1
PHF14	NM_014660.4 link	c.232G>A	p.Glu78Lys	missense_variant	3/17		NP_055475.2	O94880-1B4DG57
PHF14	NR_033435.2 link	n.564+7546G>A		intron_variant
PHF14	NR_033436.2 link	n.564+7546G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF14	ENST00000634607.2 link	c.232G>A	p.Glu78Lys	missense_variant	3/18	5	NM_001007157.2	ENSP00000489535.1		O94880-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000447

AC:

AN:

223466

Hom.:

AF XY:

0.00

AC XY:

AN XY:

120748

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000316

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.02e-7

AC:

AN:

1425426

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709260

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000236

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 19, 2024

The c.232G>A (p.E78K) alteration is located in exon 3 (coding exon 3) of the PHF14 gene. This alteration results from a G to A substitution at nucleotide position 232, causing the glutamic acid (E) at amino acid position 78 to be replaced by a lysine (K). 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

0.098

BayesDel_addAF

Benign

0.010

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

T;T

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.038

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.4

L;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.0

N;.

REVEL

Benign

0.12

Sift

Uncertain

0.0020

D;.

Polyphen

0.73

P;.

Vest4

0.11

MutPred

0.21

Gain of ubiquitination at E78 (P = 0.0114);Gain of ubiquitination at E78 (P = 0.0114);

MVP

0.68

MPC

0.036

ClinPred

0.49

GERP RS

5.1

Varity_R

0.28

gMVP

0.15

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