7-10982618-A-G

Position:

• chr7-10982618-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001007157.2(PHF14):​c.359A>G​(p.Glu120Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PHF14 NM_001007157.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25

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 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=0.0912081).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF14	NM_001007157.2	c.359A>G	p.Glu120Gly	missense_variant	3/18	ENST00000634607.2	NP_001007158.1
PHF14	NM_014660.4	c.359A>G	p.Glu120Gly	missense_variant	3/17		NP_055475.2
PHF14	NR_033435.2	n.564+7673A>G		intron_variant
PHF14	NR_033436.2	n.564+7673A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF14	ENST00000634607.2	c.359A>G	p.Glu120Gly	missense_variant	3/18	5	NM_001007157.2	ENSP00000489535.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000971 AC: 1

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

Jan 24, 2024

The c.359A>G (p.E120G) alteration is located in exon 3 (coding exon 3) of the PHF14 gene. This alteration results from a A to G substitution at nucleotide position 359, causing the glutamic acid (E) at amino acid position 120 to be replaced by a glycine (G). 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	0.097
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.026
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.88	N;.
REVEL	Benign	0.046
Sift	Uncertain	0.011	D;.
Polyphen		0.61	P;.
Vest4		0.12
MutPred		0.22		Gain of loop (P = 0.0013);Gain of loop (P = 0.0013);
MVP		0.62
MPC		0.037
ClinPred		0.23	T
GERP RS		4.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.1
Varity_R		0.080
gMVP		0.14

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

Other links and lift over

dbSNP: rs767770715; hg19: chr7-11022245;