7-10982603-A-T

Variant names:

• chr7-10982603-A-T
• rs218966
• NM_001007157.2:c.344A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001007157.2(PHF14):​c.344A>T​(p.Lys115Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000147 in 1,362,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 29)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: PHF14 NM_001007157.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.43
• Publications: 29 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31461164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF14	NM_001007157.2	c.344A>T	p.Lys115Met	missense_variant	Exon 3 of 18	ENST00000634607.2	NP_001007158.1
PHF14	NM_014660.4	c.344A>T	p.Lys115Met	missense_variant	Exon 3 of 17		NP_055475.2
PHF14	NR_033435.2	n.564+7658A>T		intron_variant	Intron 2 of 15
PHF14	NR_033436.2	n.564+7658A>T		intron_variant	Intron 2 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF14	ENST00000634607.2	c.344A>T	p.Lys115Met	missense_variant	Exon 3 of 18	5	NM_001007157.2	ENSP00000489535.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1362652 Hom.: 0 Cov.: 24 AF XY: 0.00000148 AC XY: 1 AN XY: 673986

African (AFR) AF: 0.00 AC: 0 AN: 30324

American (AMR) AF: 0.00 AC: 0 AN: 34354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24780

East Asian (EAS) AF: 0.00 AC: 0 AN: 35578

South Asian (SAS) AF: 0.00 AC: 0 AN: 76630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 0.00000191 AC: 2 AN: 1049358

Other (OTH) AF: 0.00 AC: 0 AN: 56718

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.022	T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.018
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.6	L;.
PhyloP100		4.4
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.94	N;.
REVEL	Benign	0.057
Sift	Uncertain	0.0050	D;.
Polyphen		0.12	B;.
Vest4		0.37
MutPred		0.25		Loss of methylation at K115 (P = 0.0071);Loss of methylation at K115 (P = 0.0071);
MVP		0.66
MPC		0.040
ClinPred		0.44	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.085
gMVP		0.17
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: rs218966; hg19: chr7-11022230;