rs759442715

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_018288.4(PHF10):​c.1385G>T​(p.Cys462Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PHF10
NM_018288.4 missense

Scores

14
4
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.42
Variant links:
Genes affected
PHF10 (HGNC:18250): (PHD finger protein 10) This gene contains a predicted ORF that encodes a protein with two zinc finger domains. The function of the encoded protein is not known. Sequence analysis suggests that multiple alternatively spliced transcript variants are derived from this gene but the full-length nature of only two of them is known. These two splice variants encode different isoforms. A pseudogene for this gene is located on Xq28. [provided by RefSeq, Jul 2008]
C6orf120 (HGNC:21247): (chromosome 6 open reading frame 120) This gene encodes a conserved, N-glycosylated protein that likely functions in the cellular response to endoplasmic reticulum stress. This protein is able to induce apoptosis in vitro in CD4+ T-cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.99

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PHF10NM_018288.4 linkc.1385G>T p.Cys462Phe missense_variant Exon 11 of 12 ENST00000339209.9 NP_060758.2 Q8WUB8-1
C6orf120NM_001029863.3 linkc.*2124C>A 3_prime_UTR_variant Exon 1 of 1 ENST00000332290.4 NP_001025034.1 Q7Z4R8
PHF10NM_133325.3 linkc.1379G>T p.Cys460Phe missense_variant Exon 11 of 12 NP_579866.2 Q8WUB8-2
C6orf120NM_001317342.2 linkc.*2124C>A 3_prime_UTR_variant Exon 2 of 2 NP_001304271.1 Q7Z4R8B4DJ79

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PHF10ENST00000339209.9 linkc.1385G>T p.Cys462Phe missense_variant Exon 11 of 12 1 NM_018288.4 ENSP00000341805.4 Q8WUB8-1
PHF10ENST00000621772.4 linkc.1244G>T p.Cys415Phe missense_variant Exon 11 of 12 1 ENSP00000484117.1 Q8WUB8-3
C6orf120ENST00000332290.4 linkc.*2124C>A 3_prime_UTR_variant Exon 1 of 1 6 NM_001029863.3 ENSP00000346931.1 Q7Z4R8
PHF10ENST00000366780.8 linkc.1379G>T p.Cys460Phe missense_variant Exon 11 of 12 5 ENSP00000355743.4 Q8WUB8-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000405
AC:
1
AN:
247056
Hom.:
0
AF XY:
0.00000749
AC XY:
1
AN XY:
133524
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000548
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457916
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
725042
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.47
D
BayesDel_noAF
Pathogenic
0.60
CADD
Pathogenic
31
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.58
.;D;.
Eigen
Pathogenic
1.2
Eigen_PC
Pathogenic
1.1
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Pathogenic
0.63
D
MetaRNN
Pathogenic
0.99
D;D;D
MetaSVM
Pathogenic
0.94
D
MutationAssessor
Pathogenic
4.9
.;H;.
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-9.0
D;D;.
REVEL
Pathogenic
0.94
Sift
Pathogenic
0.0
D;D;.
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.88
MutPred
0.96
.;Loss of sheet (P = 0.0817);.;
MVP
0.93
MPC
1.7
ClinPred
1.0
D
GERP RS
6.1
Varity_R
0.93
gMVP
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs759442715; hg19: chr6-170105255; API