7-10982918-A-C

Variant names:

• chr7-10982918-A-C
• NM_001007157.2:c.659A>C

Variant summary

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

The NM_001007157.2(PHF14):​c.659A>C​(p.Lys220Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,460,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000055 (0 hom.)
• Consequence: PHF14 NM_001007157.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.17

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=0.22978607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF14	NM_001007157.2	c.659A>C	p.Lys220Thr	missense_variant	Exon 3 of 18	ENST00000634607.2	NP_001007158.1
PHF14	NM_014660.4	c.659A>C	p.Lys220Thr	missense_variant	Exon 3 of 17		NP_055475.2
PHF14	NR_033435.2	n.565-7785A>C		intron_variant	Intron 2 of 15
PHF14	NR_033436.2	n.565-7785A>C		intron_variant	Intron 2 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF14	ENST00000634607.2	c.659A>C	p.Lys220Thr	missense_variant	Exon 3 of 18	5	NM_001007157.2	ENSP00000489535.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1460032 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 726116

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: 0.00000630

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.659A>C (p.K220T) alteration is located in exon 3 (coding exon 3) of the PHF14 gene. This alteration results from a A to C substitution at nucleotide position 659, causing the lysine (K) at amino acid position 220 to be replaced by a threonine (T). 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	Uncertain	0.35
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.073	T;T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.1	N;.
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D;.
Polyphen		0.91	P;.
Vest4		0.42
MutPred		0.34		Loss of methylation at K220 (P = 0.0031);Loss of methylation at K220 (P = 0.0031);
MVP		0.73
MPC		0.24
ClinPred		0.80	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.22

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: chr7-11022545;