NM_016483.7:c.169G>T

Variant summary

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

The NM_016483.7(PHF7):​c.169G>T​(p.Val57Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,310 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V57M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PHF7
NM_016483.7 missense

Scores

8
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.40
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]

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ACMG classification

Classification made for transcript

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
PHF7NM_016483.7 linkc.169G>T p.Val57Leu missense_variant Exon 4 of 11 ENST00000327906.8 NP_057567.3 Q9BWX1-1A0A024R336

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PHF7ENST00000327906.8 linkc.169G>T p.Val57Leu missense_variant Exon 4 of 11 1 NM_016483.7 ENSP00000333024.3 Q9BWX1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457310
Hom.:
0
Cov.:
28
AF XY:
0.00000138
AC XY:
1
AN XY:
725356
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.47
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.030
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.034
T;.;.;.
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.094
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.78
T;.;T;T
M_CAP
Benign
0.049
D
MetaRNN
Uncertain
0.53
D;D;D;D
MetaSVM
Uncertain
-0.11
T
MutationAssessor
Benign
1.9
L;L;L;.
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-1.6
N;N;.;.
REVEL
Uncertain
0.50
Sift
Benign
0.11
T;T;.;.
Sift4G
Benign
0.084
T;T;T;T
Polyphen
0.0020
B;.;.;.
Vest4
0.50
MutPred
0.67
Loss of methylation at K52 (P = 0.0694);Loss of methylation at K52 (P = 0.0694);Loss of methylation at K52 (P = 0.0694);.;
MVP
0.86
MPC
0.24
ClinPred
0.36
T
GERP RS
2.3
Varity_R
0.10
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.18
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: chr3-52448586; API