Variant 6-169721071-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018288.4(PHF10):c.128C>T(p.Ser43Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,546,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000093 ( 0 hom. )

Consequence

PHF10
NM_018288.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.29

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]

PHF10 links:

PHF10 (HGNC:):

PHF10 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1486181).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF10	NM_018288.4 linkuse as main transcript	c.128C>T	p.Ser43Phe	missense_variant	2/12	ENST00000339209.9	NP_060758.2	Q8WUB8-1
PHF10	NM_133325.3 linkuse as main transcript	c.128C>T	p.Ser43Phe	missense_variant	2/12		NP_579866.2	Q8WUB8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF10	ENST00000339209.9 linkuse as main transcript	c.128C>T	p.Ser43Phe	missense_variant	2/12	1	NM_018288.4	ENSP00000341805.4		Q8WUB8-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152092

Hom.:

Cov.:

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:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000932

AC:

AN:

1394132

Hom.:

Cov.:

AF XY:

0.00000727

AC XY:

AN XY:

687856

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000121

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74276

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:

0.0000712

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.128C>T (p.S43F) alteration is located in exon 2 (coding exon 2) of the PHF10 gene. This alteration results from a C to T substitution at nucleotide position 128, causing the serine (S) at amino acid position 43 to be replaced by a phenylalanine (F). 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

Benign

0.25

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.059

.;T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.019

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;.

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.7

N;N;.

REVEL

Benign

0.080

Sift

Benign

0.046

D;D;.

Sift4G

Benign

0.067

T;T;T

Polyphen

0.37

B;B;.

Vest4

0.39

MutPred

0.18

Loss of phosphorylation at S43 (P = 0.0069);Loss of phosphorylation at S43 (P = 0.0069);Loss of phosphorylation at S43 (P = 0.0069);

MVP

0.56

MPC

0.61

ClinPred

0.26

GERP RS

3.6

Varity_R

0.081

gMVP

0.41

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over