3-52419875-G-C

Variant names:

• chr3-52419875-G-C
• rs999188722
• NM_016483.7:c.229G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016483.7(PHF7):​c.229G>C​(p.Gly77Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,112 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 30)
• Consequence: PHF7 NM_016483.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00
• Publications: 0 publications found

Genes affected

PHF7 (HGNC:18458): (PHD finger protein 7) Spermatogenesis is a complex process regulated by extracellular and intracellular factors as well as cellular interactions among interstitial cells of the testis, Sertoli cells, and germ cells. This gene is expressed in the testis in Sertoli cells but not germ cells. The protein encoded by this gene contains plant homeodomain (PHD) finger domains, also known as leukemia associated protein (LAP) domains, believed to be involved in transcriptional regulation. The protein, which localizes to the nucleus of transfected cells, has been implicated in the transcriptional regulation of spermatogenesis. Alternate splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016483.7. 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
	PHF7	NM_016483.7	MANE Select	c.229G>C	p.Gly77Arg	missense	Exon 5 of 11	NP_057567.3
	PHF7	NM_001321126.2		c.229G>C	p.Gly77Arg	missense	Exon 5 of 11	NP_001308055.1	Q9BWX1-1
	PHF7	NM_001321127.2		c.229G>C	p.Gly77Arg	missense	Exon 5 of 11	NP_001308056.1	Q9BWX1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF7	ENST00000327906.8	TSL:1 MANE Select	c.229G>C	p.Gly77Arg	missense	Exon 5 of 11	ENSP00000333024.3	Q9BWX1-1
	PHF7	ENST00000614886.4	TSL:1	c.229G>C	p.Gly77Arg	missense	Exon 4 of 9	ENSP00000480003.1	Q9BWX1-2
	PHF7	ENST00000894733.1		c.229G>C	p.Gly77Arg	missense	Exon 5 of 11	ENSP00000564792.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152112 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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.: 28

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152112 Hom.: 0 Cov.: 30 AF XY: 0.0000269 AC XY: 2 AN XY: 74292

African (AFR) AF: 0.00 AC: 0 AN: 41408

American (AMR) AF: 0.000131 AC: 2 AN: 15260

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.17	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	0.46	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.0
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-7.7	D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.57
MutPred		0.54		Gain of glycosylation at S74 (P = 0.011)
MVP		0.97
MPC		0.95
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.86
gMVP		0.75
Mutation Taster		=70/30	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: rs999188722; hg19: chr3-52453891;