Genetic Variant PHF10:p.Asn406Asn (chr6-169705620-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_018288.4(PHF10):c.1218T>C(p.Asn406Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000162 in 1,233,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

PHF10
NM_018288.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.66

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 Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 6-169705620-A-G is Benign according to our data. Variant chr6-169705620-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2657145.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.66 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF10	NM_018288.4 link	c.1218T>C	p.Asn406Asn	synonymous_variant	Exon 10 of 12	ENST00000339209.9	NP_060758.2	Q8WUB8-1
C6orf120	NM_001029863.3 link	c.*2585A>G		3_prime_UTR_variant	Exon 1 of 1	ENST00000332290.4	NP_001025034.1	Q7Z4R8
PHF10	NM_133325.3 link	c.1212T>C	p.Asn404Asn	synonymous_variant	Exon 10 of 12		NP_579866.2	Q8WUB8-2
C6orf120	NM_001317342.2 link	c.*2585A>G		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.1218T>C	p.Asn406Asn	synonymous_variant	Exon 10 of 12	1	NM_018288.4	ENSP00000341805.4	Q8WUB8-1
PHF10	ENST00000621772.4 link	c.1077T>C	p.Asn359Asn	synonymous_variant	Exon 10 of 12	1		ENSP00000484117.1	Q8WUB8-3
C6orf120	ENST00000332290.4 link	c.*2585A>G		3_prime_UTR_variant	Exon 1 of 1	6	NM_001029863.3	ENSP00000346931.1	Q7Z4R8
PHF10	ENST00000366780.8 link	c.1212T>C	p.Asn404Asn	synonymous_variant	Exon 10 of 12	5		ENSP00000355743.4	Q8WUB8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250556

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135536

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000162

AC:

AN:

1233200

Hom.:

Cov.:

AF XY:

0.00000160

AC XY:

AN XY:

625538

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:

0.00000221

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PHF10: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.5

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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