rs35491443

Variant names:

• chr3-52422817-C-T
• rs35491443
• NM_016483.7:c.855C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.609
• Publications: 7 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: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.855C>T	p.Cys285Cys	synonymous	Exon 10 of 11	NP_057567.3
	PHF7	NM_001321126.2		c.855C>T	p.Cys285Cys	synonymous	Exon 10 of 11	NP_001308055.1	Q9BWX1-1
	PHF7	NM_001321127.2		c.855C>T	p.Cys285Cys	synonymous	Exon 10 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.855C>T	p.Cys285Cys	synonymous	Exon 10 of 11	ENSP00000333024.3	Q9BWX1-1
	PHF7	ENST00000614886.4	TSL:1	c.738C>T	p.Cys246Cys	synonymous	Exon 8 of 9	ENSP00000480003.1	Q9BWX1-2
	PHF7	ENST00000498509.2	TSL:1	n.1470C>T		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes AF: 0.00386 AC: 587 AN: 152162 Hom.: 4 Cov.: 32

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

GnomAD2 exomes AF: 0.00595 AC: 1497 AN: 251416 AF XY: 0.00699

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 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.: 67 Cov.: 31 AF XY: 0.00640 AC XY: 4651 AN XY: 727140

African (AFR) AF: 0.000627 AC: 21 AN: 33478

American (AMR) AF: 0.00224 AC: 100 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00161 AC: 42 AN: 26136

East Asian (EAS) AF: 0.00786 AC: 312 AN: 39700

South Asian (SAS) AF: 0.0235 AC: 2024 AN: 86252

European-Finnish (FIN) AF: 0.00152 AC: 81 AN: 53420

Middle Eastern (MID) AF: 0.00520 AC: 30 AN: 5768

European-Non Finnish (NFE) AF: 0.00507 AC: 5632 AN: 1111800

Other (OTH) AF: 0.00560 AC: 338 AN: 60388

GnomAD4 genome AF: 0.00385 AC: 586 AN: 152280 Hom.: 4 Cov.: 32 AF XY: 0.00403 AC XY: 300 AN XY: 74466

African (AFR) AF: 0.000866 AC: 36 AN: 41548

American (AMR) AF: 0.00314 AC: 48 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00771 AC: 40 AN: 5188

South Asian (SAS) AF: 0.0233 AC: 112 AN: 4816

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00472 AC: 321 AN: 68018

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00367 Hom.: 2

Bravo AF: 0.00306

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00493 AC: 19

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00419 AC: 36

ExAC AF: 0.00632 AC: 767

Asia WGS AF: 0.0100 AC: 36 AN: 3478

EpiCase AF: 0.00403

EpiControl AF: 0.00498

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.46
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-0.70	T
PhyloP100		0.61
Vest4		0.23
MVP		0.52
ClinPred		0.0093	T
GERP RS		1.9
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs35491443; hg19: chr3-52456833; COSMIC: COSV107394569; COSMIC: COSV107394569;