7-10983030-A-T

Position:

• chr7-10983030-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001007157.2(PHF14):​c.771A>T​(p.Glu257Asp) 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. 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)
• Consequence: PHF14 NM_001007157.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.326

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031355858).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF14	NM_001007157.2	c.771A>T	p.Glu257Asp	missense_variant	3/18	ENST00000634607.2	NP_001007158.1
PHF14	NM_014660.4	c.771A>T	p.Glu257Asp	missense_variant	3/17		NP_055475.2
PHF14	NR_033435.2	n.565-7673A>T		intron_variant
PHF14	NR_033436.2	n.565-7673A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF14	ENST00000634607.2	c.771A>T	p.Glu257Asp	missense_variant	3/18	5	NM_001007157.2	ENSP00000489535.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2023

The c.771A>T (p.E257D) alteration is located in exon 3 (coding exon 3) of the PHF14 gene. This alteration results from a A to T substitution at nucleotide position 771, causing the glutamic acid (E) at amino acid position 257 to be replaced by an aspartic acid (D). 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	0.060
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	10
DANN	Benign	0.73
DEOGEN2	Benign	0.010	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.031	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.14	N;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.33	N;.
REVEL	Benign	0.14
Sift	Benign	0.43	T;.
Polyphen		0.0	B;.
Vest4		0.055
MutPred		0.18		Loss of solvent accessibility (P = 0.1177);Loss of solvent accessibility (P = 0.1177);
MVP		0.31
MPC		0.032
ClinPred		0.081	T
GERP RS		-2.2
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.9
Varity_R		0.018
gMVP		0.041

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-11022657;