Genetic Variant PHF7:p.Cys285Cys (chr3-52422817-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_016483.7(PHF7):c.855C>T(p.Cys285Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00568 in 1,613,946 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 67 hom. )

Consequence

PHF7
NM_016483.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.609

Variant links:

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]

PHF7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003453195).

BP6

Variant 3-52422817-C-T is Benign according to our data. Variant chr3-52422817-C-T is described in ClinVar as [Benign]. Clinvar id is 776464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.609 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00385 (586/152280) while in subpopulation SAS AF= 0.0233 (112/4816). AF 95% confidence interval is 0.0198. There are 4 homozygotes in gnomad4. There are 300 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF7	NM_016483.7 link	c.855C>T	p.Cys285Cys	synonymous_variant	Exon 10 of 11	ENST00000327906.8	NP_057567.3	Q9BWX1-1A0A024R336

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF7	ENST00000327906.8 link	c.855C>T	p.Cys285Cys	synonymous_variant	Exon 10 of 11	1	NM_016483.7	ENSP00000333024.3		Q9BWX1-1

Frequencies

GnomAD3 genomes

AF:

0.00386

AC:

587

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00769

Gnomad SAS

AF:

0.0234

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00473

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00595

AC:

1497

AN:

251416

Hom.:

AF XY:

0.00699

AC XY:

950

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00772

Gnomad SAS exome

AF:

0.0233

Gnomad FIN exome

AF:

0.00157

Gnomad NFE exome

AF:

0.00419

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00587

AC:

8580

AN:

1461666

Hom.:

Cov.:

AF XY:

0.00640

AC XY:

4651

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.00786

Gnomad4 SAS exome

AF:

0.0235

Gnomad4 FIN exome

AF:

0.00152

Gnomad4 NFE exome

AF:

0.00507

Gnomad4 OTH exome

AF:

0.00560

GnomAD4 genome

AF:

0.00385

AC:

586

AN:

152280

Hom.:

Cov.:

AF XY:

0.00403

AC XY:

300

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00771

Gnomad4 SAS

AF:

0.0233

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00472

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00343

Hom.:

Bravo

AF:

0.00306

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00632

AC:

767

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.00403

EpiControl

AF:

0.00498

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.46

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0035

MetaSVM

Benign

-0.70

Vest4

0.23

MVP

0.52

ClinPred

0.0093

GERP RS

1.9

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over