rs138138680

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_018288.4(PHF10):c.1327C>T(p.His443Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,613,640 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 2 hom. )

Consequence

PHF10
NM_018288.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.41

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:

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]

C6orf120 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019065797).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF10	NM_018288.4 link	c.1327C>T	p.His443Tyr	missense_variant	Exon 11 of 12	ENST00000339209.9	NP_060758.2	Q8WUB8-1
C6orf120	NM_001029863.3 link	c.*2182G>A		3_prime_UTR_variant	Exon 1 of 1	ENST00000332290.4	NP_001025034.1	Q7Z4R8
PHF10	NM_133325.3 link	c.1321C>T	p.His441Tyr	missense_variant	Exon 11 of 12		NP_579866.2	Q8WUB8-2
C6orf120	NM_001317342.2 link	c.*2182G>A		3_prime_UTR_variant	Exon 2 of 2		NP_001304271.1	Q7Z4R8B4DJ79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PHF10	ENST00000339209.9 link	c.1327C>T	p.His443Tyr	missense_variant	Exon 11 of 12	1	NM_018288.4	ENSP00000341805.4	Q8WUB8-1
PHF10	ENST00000621772.4 link	c.1186C>T	p.His396Tyr	missense_variant	Exon 11 of 12	1		ENSP00000484117.1	Q8WUB8-3
C6orf120	ENST00000332290.4 link	c.*2182G>A		3_prime_UTR_variant	Exon 1 of 1	6	NM_001029863.3	ENSP00000346931.1	Q7Z4R8
PHF10	ENST00000366780.8 link	c.1321C>T	p.His441Tyr	missense_variant	Exon 11 of 12	5		ENSP00000355743.4	Q8WUB8-2

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

193

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00165

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00133

AC:

334

AN:

250650

Hom.:

AF XY:

0.00114

AC XY:

154

AN XY:

135580

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00321

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00172

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00165

AC:

2411

AN:

1461406

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

1180

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00302

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000375

Gnomad4 NFE exome

AF:

0.00195

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00127

AC:

193

AN:

152234

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.00165

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00142

Hom.:

Bravo

AF:

0.00142

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00110

AC:

133

EpiCase

AF:

0.00153

EpiControl

AF:

0.00148

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1327C>T (p.H443Y) alteration is located in exon 11 (coding exon 11) of the PHF10 gene. This alteration results from a C to T substitution at nucleotide position 1327, causing the histidine (H) at amino acid position 443 to be replaced by a tyrosine (Y). 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

0.23

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.035

.;T;.

Eigen

Uncertain

0.57

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.019

T;T;T

MetaSVM

Uncertain

0.26

MutationAssessor

Benign

1.0

.;L;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.94

N;N;.

REVEL

Uncertain

0.60

Sift

Benign

0.72

T;T;.

Sift4G

Benign

0.99

T;T;T

Polyphen

1.0

D;B;.

Vest4

0.74

MVP

0.71

MPC

0.84

ClinPred

0.049

GERP RS

5.8

Varity_R

0.22

gMVP

0.61

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.

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