NM_001007157.2:c.659A>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22978607).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007157.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF14	NM_001007157.2	MANE Select	c.659A>C	p.Lys220Thr	missense	Exon 3 of 18	NP_001007158.1	O94880-3
	PHF14	NM_014660.4		c.659A>C	p.Lys220Thr	missense	Exon 3 of 17	NP_055475.2
	PHF14	NR_033435.2		n.565-7785A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF14	ENST00000634607.2	TSL:5 MANE Select	c.659A>C	p.Lys220Thr	missense	Exon 3 of 18	ENSP00000489535.1	O94880-3
	PHF14	ENST00000403050.7	TSL:1	c.659A>C	p.Lys220Thr	missense	Exon 3 of 17	ENSP00000385795.3	O94880-1
	PHF14	ENST00000931753.1		c.659A>C	p.Lys220Thr	missense	Exon 4 of 19	ENSP00000601812.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1110928

Other (OTH) AF: 0.0000166 AC: 1 AN: 60330

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.90	L
PhyloP100		5.2
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)
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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr7-11022545;