dbSNP rs373121095: PHF10:p.Ile379Leu (chr6-169705703-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_018288.4(PHF10):c.1135A>T(p.Ile379Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

PHF10
NM_018288.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.71

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:

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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=0.083982885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF10	NM_018288.4 link	c.1135A>T	p.Ile379Leu	missense_variant	Exon 10 of 12	ENST00000339209.9	NP_060758.2	Q8WUB8-1
C6orf120	NM_001029863.3 link	c.*2668T>A		3_prime_UTR_variant	Exon 1 of 1	ENST00000332290.4	NP_001025034.1	Q7Z4R8
PHF10	NM_133325.3 link	c.1129A>T	p.Ile377Leu	missense_variant	Exon 10 of 12		NP_579866.2	Q8WUB8-2
C6orf120	NM_001317342.2 link	c.*2668T>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.1135A>T	p.Ile379Leu	missense_variant	Exon 10 of 12	1	NM_018288.4	ENSP00000341805.4	Q8WUB8-1
PHF10	ENST00000621772.4 link	c.994A>T	p.Ile332Leu	missense_variant	Exon 10 of 12	1		ENSP00000484117.1	Q8WUB8-3
C6orf120	ENST00000332290.4 link	c.*2668T>A		3_prime_UTR_variant	Exon 1 of 1	6	NM_001029863.3	ENSP00000346931.1	Q7Z4R8
PHF10	ENST00000366780.8 link	c.1129A>T	p.Ile377Leu	missense_variant	Exon 10 of 12	5		ENSP00000355743.4	Q8WUB8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.071

.;T;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.084

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.85

.;L;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.26

N;N;.

REVEL

Benign

0.27

Sift

Benign

0.56

T;T;.

Sift4G

Benign

0.42

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.13

MutPred

0.48

.;Gain of loop (P = 0.0851);.;

MVP

0.51

MPC

0.47

ClinPred

0.35

GERP RS

-0.44

Varity_R

0.062

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over