6-169704085-C-T

Position:

chr6-169704085-C-T

Variant summary

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

The ENST00000339209.9(PHF10):c.1415G>A(p.Arg472His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000362 in 1,573,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R472L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

PHF10
ENST00000339209.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

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 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=0.2258035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PHF10	NM_018288.4 linkuse as main transcript	c.1415G>A	p.Arg472His	missense_variant	12/12	ENST00000339209.9	NP_060758.2
C6orf120	NM_001029863.3 linkuse as main transcript	c.*1050C>T		3_prime_UTR_variant	1/1	ENST00000332290.4	NP_001025034.1
PHF10	NM_133325.3 linkuse as main transcript	c.1409G>A	p.Arg470His	missense_variant	12/12		NP_579866.2
C6orf120	NM_001317342.2 linkuse as main transcript	c.*1050C>T		3_prime_UTR_variant	2/2		NP_001304271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF10	ENST00000339209.9 linkuse as main transcript	c.1415G>A	p.Arg472His	missense_variant	12/12	1	NM_018288.4	ENSP00000341805		Q8WUB8-1
PHF10	ENST00000621772.4 linkuse as main transcript	c.1274G>A	p.Arg425His	missense_variant	12/12	1		ENSP00000484117	P1	Q8WUB8-3
C6orf120	ENST00000332290.4 linkuse as main transcript	c.*1050C>T		3_prime_UTR_variant	1/1		NM_001029863.3	ENSP00000346931	P1
PHF10	ENST00000366780.8 linkuse as main transcript	c.1409G>A	p.Arg470His	missense_variant	12/12	5		ENSP00000355743		Q8WUB8-2

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000247

AC:

AN:

210584

Hom.:

AF XY:

0.000287

AC XY:

AN XY:

114884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000190

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000427

Gnomad OTH exome

AF:

0.000204

GnomAD4 exome

AF:

0.000369

AC:

525

AN:

1421054

Hom.:

Cov.:

AF XY:

0.000357

AC XY:

252

AN XY:

706774

show subpopulations

Gnomad4 AFR exome

AF:

0.0000327

Gnomad4 AMR exome

AF:

0.000192

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000153

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000425

Gnomad4 OTH exome

AF:

0.000358

GnomAD4 genome

AF:

0.000296

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000574

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000238

Hom.:

Bravo

AF:

0.000264

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000296

AC:

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

Feb 28, 2023

The c.1415G>A (p.R472H) alteration is located in exon 12 (coding exon 12) of the PHF10 gene. This alteration results from a G to A substitution at nucleotide position 1415, causing the arginine (R) at amino acid position 472 to be replaced by a histidine (H). 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

0.12

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

.;T;.

Eigen

Benign

-0.0054

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.45

MutationAssessor

Benign

1.1

.;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.9

N;N;.

REVEL

Benign

0.25

Sift

Benign

0.17

T;T;.

Sift4G

Benign

0.27

T;T;T

Polyphen

0.025

B;P;.

Vest4

0.46

MVP

0.73

MPC

0.64

ClinPred

0.033

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.20

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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