7-10983007-G-A

Variant names:

• chr7-10983007-G-A
• rs1446533773
• NM_001007157.2:c.748G>A

Variant summary

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

The NM_001007157.2(PHF14):​c.748G>A​(p.Glu250Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000559 in 1,430,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: PHF14 NM_001007157.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79

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=0.1667977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF14	NM_001007157.2	c.748G>A	p.Glu250Lys	missense_variant	Exon 3 of 18	ENST00000634607.2	NP_001007158.1
PHF14	NM_014660.4	c.748G>A	p.Glu250Lys	missense_variant	Exon 3 of 17		NP_055475.2
PHF14	NR_033435.2	n.565-7696G>A		intron_variant	Intron 2 of 15
PHF14	NR_033436.2	n.565-7696G>A		intron_variant	Intron 2 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF14	ENST00000634607.2	c.748G>A	p.Glu250Lys	missense_variant	Exon 3 of 18	5	NM_001007157.2	ENSP00000489535.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000559 AC: 8 AN: 1430982 Hom.: 0 Cov.: 33 AF XY: 0.00000282 AC XY: 2 AN XY: 709336

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.000134

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.748G>A (p.E250K) 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 748, causing the glutamic acid (E) at amino acid position 250 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	0.16
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T;T
Eigen	Benign	0.027
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.8	N;.
REVEL	Benign	0.10
Sift	Uncertain	0.0060	D;.
Polyphen		0.43	B;.
Vest4		0.23
MutPred		0.20		Gain of ubiquitination at E250 (P = 0.017);Gain of ubiquitination at E250 (P = 0.017);
MVP		0.74
MPC		0.040
ClinPred		0.53	D
GERP RS		4.8
Varity_R		0.15
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: rs1446533773; hg19: chr7-11022634; COSMIC: COSV68857181;