3-52421648-A-G

Variant names:

• chr3-52421648-A-G
• NM_016483.7:c.574A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016483.7(PHF7):​c.574A>G​(p.Lys192Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHF7 NM_016483.7 missense, splice_region
• Scores: Splicing: ADA: 0.001255
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF7	NM_016483.7	c.574A>G	p.Lys192Glu	missense_variant, splice_region_variant	Exon 8 of 11	ENST00000327906.8	NP_057567.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF7	ENST00000327906.8	c.574A>G	p.Lys192Glu	missense_variant, splice_region_variant	Exon 8 of 11	1	NM_016483.7	ENSP00000333024.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.574A>G (p.K192E) alteration is located in exon 8 (coding exon 7) of the PHF7 gene. This alteration results from a A to G substitution at nucleotide position 574, causing the lysine (K) at amino acid position 192 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T;.;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.80	T;.;T
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Uncertain	0.077	D
MutationAssessor	Benign	1.7	L;L;L
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.90	N;N;.
REVEL	Uncertain	0.42
Sift	Benign	0.32	T;T;.
Sift4G	Benign	0.12	T;D;D
Polyphen		0.89	P;.;.
Vest4		0.54
MutPred		0.44		Loss of MoRF binding (P = 0.005);Loss of MoRF binding (P = 0.005);Loss of MoRF binding (P = 0.005);
MVP		0.87
MPC		0.81
ClinPred		0.74	D
GERP RS		4.8
Varity_R		0.16
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0013
dbscSNV1_RF	Benign	0.016
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-52455664;