7-10983047-C-T

Variant names:

• chr7-10983047-C-T
• rs1339818211
• NM_001007157.2:c.788C>T

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.788C>T​(p.Ala263Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: PHF14 NM_001007157.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.78
• 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=0.09700948).

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.788C>T	p.Ala263Val	missense	Exon 3 of 18	NP_001007158.1	O94880-3
	PHF14	NM_014660.4		c.788C>T	p.Ala263Val	missense	Exon 3 of 17	NP_055475.2
	PHF14	NR_033435.2		n.565-7656C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF14	ENST00000634607.2	TSL:5 MANE Select	c.788C>T	p.Ala263Val	missense	Exon 3 of 18	ENSP00000489535.1	O94880-3
	PHF14	ENST00000403050.7	TSL:1	c.788C>T	p.Ala263Val	missense	Exon 3 of 17	ENSP00000385795.3	O94880-1
	PHF14	ENST00000931753.1		c.788C>T	p.Ala263Val	missense	Exon 4 of 19	ENSP00000601812.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152010 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152010 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74236

African (AFR) AF: 0.0000242 AC: 1 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Benign	0.081
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.075
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.8
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.071
Sift	Uncertain	0.010	D
Polyphen		0.0	B
Vest4		0.077
MutPred		0.17		Gain of MoRF binding (P = 0.1388)
MVP		0.36
MPC		0.050
ClinPred		0.52	D
GERP RS		4.1
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
Varity_R		0.066
gMVP		0.089
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

dbSNP: rs1339818211; hg19: chr7-11022674;