rs218966

Positions:

• chr7-10982603-A-G
• chr7-10982603-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001007157.2(PHF14):​c.344A>G​(p.Lys115Arg) variant causes a missense change. The variant allele was found at a frequency of 0.645 in 1,513,036 control chromosomes in the GnomAD database, including 316,826 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.68 (35106 hom., cov: 29)
  • Exomes 𝑓: 0.64 (281720 hom.)
• Consequence: PHF14 NM_001007157.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.43

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.013119E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF14	NM_001007157.2	c.344A>G	p.Lys115Arg	missense_variant	3/18	ENST00000634607.2
PHF14	NM_014660.4	c.344A>G	p.Lys115Arg	missense_variant	3/17
PHF14	NR_033435.2	n.564+7658A>G		intron_variant, non_coding_transcript_variant
PHF14	NR_033436.2	n.564+7658A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF14	ENST00000634607.2	c.344A>G	p.Lys115Arg	missense_variant	3/18	5	NM_001007157.2	P1

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102489 AN: 151546 Hom.: 35046 Cov.: 29

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.641

GnomAD3 exomes AF: 0.640 AC: 98392 AN: 153668 Hom.: 31993 AF XY: 0.636 AC XY: 51535 AN XY: 80978

Gnomad AFR exome AF: 0.773

Gnomad AMR exome AF: 0.601

Gnomad ASJ exome AF: 0.701

Gnomad EAS exome AF: 0.467

Gnomad SAS exome AF: 0.581

Gnomad FIN exome AF: 0.750

Gnomad NFE exome AF: 0.648

Gnomad OTH exome AF: 0.672

GnomAD4 exome AF: 0.641 AC: 872760 AN: 1361372 Hom.: 281720 Cov.: 24 AF XY: 0.640 AC XY: 430646 AN XY: 673370

Gnomad4 AFR exome AF: 0.762

Gnomad4 AMR exome AF: 0.602

Gnomad4 ASJ exome AF: 0.696

Gnomad4 EAS exome AF: 0.510

Gnomad4 SAS exome AF: 0.569

Gnomad4 FIN exome AF: 0.743

Gnomad4 NFE exome AF: 0.642

Gnomad4 OTH exome AF: 0.639

GnomAD4 genome AF: 0.677 AC: 102611 AN: 151664 Hom.: 35106 Cov.: 29 AF XY: 0.680 AC XY: 50384 AN XY: 74132

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.643

Alfa AF: 0.645 Hom.: 43597

Bravo AF: 0.669

TwinsUK AF: 0.643 AC: 2386

ALSPAC AF: 0.636 AC: 2452

ESP6500AA AF: 0.775 AC: 2717

ESP6500EA AF: 0.665 AC: 5234

ExAC AF: 0.544 AC: 44841

Asia WGS AF: 0.552 AC: 1919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.0098	T;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.092
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.80	T;T
MetaRNN	Benign	0.0000010	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N;.
MutationTaster	Benign	2.7e-13	P
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.30	N;.
REVEL	Benign	0.12
Sift	Benign	0.26	T;.
Polyphen		0.0	B;.
Vest4		0.050
MPC		0.030
ClinPred		0.0095	T
GERP RS		4.0
Varity_R		0.040
gMVP		0.040

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: rs218966; hg19: chr7-11022230; COSMIC: COSV68854441;