rs753254673

Variant names:

• chr3-52420941-A-C
• rs753254673
• NM_016483.7:c.452A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-52420941-A-C
• chr3-52420941-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016483.7(PHF7):​c.452A>C​(p.Gln151Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 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. Q151R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PHF7 NM_016483.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10975495).

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.452A>C	p.Gln151Pro	missense	Exon 7 of 11	NP_057567.3
	PHF7	NM_001321126.2		c.452A>C	p.Gln151Pro	missense	Exon 7 of 11	NP_001308055.1	Q9BWX1-1
	PHF7	NM_001321127.2		c.452A>C	p.Gln151Pro	missense	Exon 7 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.452A>C	p.Gln151Pro	missense	Exon 7 of 11	ENSP00000333024.3	Q9BWX1-1
	PHF7	ENST00000614886.4	TSL:1	c.452A>C	p.Gln151Pro	missense	Exon 6 of 9	ENSP00000480003.1	Q9BWX1-2
	PHF7	ENST00000498509.2	TSL:1	n.179A>C		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461098 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726882

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 86158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

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

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111560

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	14
DANN	Benign	0.88
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.42	T
PhyloP100		1.9
Sift4G	Benign	0.10	T
Vest4		0.20
MVP		0.39
ClinPred		0.14	T
GERP RS		2.1
PromoterAI		0.019	Neutral
Varity_R		0.095
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs753254673; hg19: chr3-52454957;