3-52414022-C-G

Variant names:

• chr3-52414022-C-G
• rs201971017
• NM_016483.7:c.68C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016483.7(PHF7):​c.68C>G​(p.Thr23Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000617 in 1,459,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: PHF7 NM_016483.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.111
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07699397).

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.68C>G	p.Thr23Ser	missense	Exon 3 of 11	NP_057567.3
	PHF7	NM_001321126.2		c.68C>G	p.Thr23Ser	missense	Exon 3 of 11	NP_001308055.1	Q9BWX1-1
	PHF7	NM_001321127.2		c.68C>G	p.Thr23Ser	missense	Exon 3 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.68C>G	p.Thr23Ser	missense	Exon 3 of 11	ENSP00000333024.3	Q9BWX1-1
	PHF7	ENST00000614886.4	TSL:1	c.68C>G	p.Thr23Ser	missense	Exon 2 of 9	ENSP00000480003.1	Q9BWX1-2
	PHF7	ENST00000894733.1		c.68C>G	p.Thr23Ser	missense	Exon 3 of 11	ENSP00000564792.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251412 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000617 AC: 9 AN: 1459374 Hom.: 0 Cov.: 28 AF XY: 0.00000551 AC XY: 4 AN XY: 726270

African (AFR) AF: 0.00 AC: 0 AN: 33422

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109744

Other (OTH) AF: 0.00 AC: 0 AN: 60330

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.083
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	7.5
DANN	Benign	0.95
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.11
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.15
Sift	Benign	0.15	T
Sift4G	Benign	0.38	T
Polyphen		0.10	B
Vest4		0.25
MutPred		0.27		Gain of glycosylation at T23 (P = 0.005)
MVP		0.73
MPC		0.22
ClinPred		0.027	T
GERP RS		2.0
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.056
gMVP		0.21
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs201971017; hg19: chr3-52448038;