7-10983023-A-G

Variant names:

• chr7-10983023-A-G
• rs749980412
• NM_001007157.2:c.764A>G

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.764A>G​(p.Asn255Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000378 in 1,587,472 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N255I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: PHF14 NM_001007157.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75
• 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=0.093198925).

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.764A>G	p.Asn255Ser	missense	Exon 3 of 18	NP_001007158.1	O94880-3
	PHF14	NM_014660.4		c.764A>G	p.Asn255Ser	missense	Exon 3 of 17	NP_055475.2
	PHF14	NR_033435.2		n.565-7680A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF14	ENST00000634607.2	TSL:5 MANE Select	c.764A>G	p.Asn255Ser	missense	Exon 3 of 18	ENSP00000489535.1	O94880-3
	PHF14	ENST00000403050.7	TSL:1	c.764A>G	p.Asn255Ser	missense	Exon 3 of 17	ENSP00000385795.3	O94880-1
	PHF14	ENST00000931753.1		c.764A>G	p.Asn255Ser	missense	Exon 4 of 19	ENSP00000601812.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000240 AC: 5 AN: 208308 AF XY: 0.00000888

Gnomad AFR exome AF: 0.0000760

Gnomad AMR exome AF: 0.0000329

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000321

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000404 AC: 58 AN: 1435316 Hom.: 0 Cov.: 32 AF XY: 0.0000323 AC XY: 23 AN XY: 712122

African (AFR) AF: 0.0000301 AC: 1 AN: 33170

American (AMR) AF: 0.0000243 AC: 1 AN: 41206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25732

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39172

South Asian (SAS) AF: 0.00 AC: 0 AN: 83706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000481 AC: 53 AN: 1102140

Other (OTH) AF: 0.0000334 AC: 2 AN: 59794

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152156 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74342

African (AFR) AF: 0.0000241 AC: 1 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15270

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.088
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.7
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.029
Sift	Benign	0.18	T
Polyphen		0.016	B
Vest4		0.17
MutPred		0.28		Gain of phosphorylation at N255 (P = 2e-04)
MVP		0.57
MPC		0.032
ClinPred		0.019	T
GERP RS		4.6
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.9
Varity_R		0.034
gMVP		0.029
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: rs749980412; hg19: chr7-11022650;