rs753391887

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016483.7(PHF7):​c.583C>T​(p.His195Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000195 in 1,592,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

PHF7
NM_016483.7 missense

Scores

1
7
11

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.48
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41786718).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PHF7NM_016483.7 linkuse as main transcriptc.583C>T p.His195Tyr missense_variant 8/11 ENST00000327906.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PHF7ENST00000327906.8 linkuse as main transcriptc.583C>T p.His195Tyr missense_variant 8/111 NM_016483.7 P1Q9BWX1-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152208
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251390
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135864
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000187
AC:
27
AN:
1440296
Hom.:
0
Cov.:
26
AF XY:
0.0000139
AC XY:
10
AN XY:
717946
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000183
Gnomad4 OTH exome
AF:
0.0000502
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152326
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000772
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Progressive sensorineural hearing impairment Uncertain:1
Uncertain significance, no assertion criteria providedresearchOtology & Neurotology- Genomics of vestibular disorders (CTS-495), Jose Antonio López Escámez, Centro Pfizer - Universidad de Granada - Junta de Andalucía de Genómica e Investigación Oncológica (GENYO)Sep 03, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
0.0
CADD
Benign
21
DANN
Benign
0.77
DEOGEN2
Benign
0.014
T;.;.
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.85
T;.;D
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.42
T;T;T
MetaSVM
Uncertain
-0.14
T
MutationAssessor
Benign
1.7
L;L;L
MutationTaster
Benign
0.96
D;D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-0.93
N;N;.
REVEL
Uncertain
0.32
Sift
Benign
1.0
T;T;.
Sift4G
Benign
1.0
T;T;T
Polyphen
0.99
D;.;.
Vest4
0.54
MutPred
0.36
Loss of disorder (P = 0.0517);Loss of disorder (P = 0.0517);Loss of disorder (P = 0.0517);
MVP
0.87
MPC
0.93
ClinPred
0.29
T
GERP RS
6.0
Varity_R
0.13
gMVP
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
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

LitVar

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

Other links and lift over

dbSNP: rs753391887; hg19: chr3-52455673; API