6-169718825-T-G

Position:

• chr6-169718825-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000339209.9(PHF10):​c.288A>C​(p.Glu96Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PHF10 ENST00000339209.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.792

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF10	NM_018288.4	c.288A>C	p.Glu96Asp	missense_variant	3/12	ENST00000339209.9	NP_060758.2
PHF10	NM_133325.3	c.288A>C	p.Glu96Asp	missense_variant	3/12		NP_579866.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF10	ENST00000339209.9	c.288A>C	p.Glu96Asp	missense_variant	3/12	1	NM_018288.4	ENSP00000341805

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

The c.288A>C (p.E96D) alteration is located in exon 3 (coding exon 3) of the PHF10 gene. This alteration results from a A to C substitution at nucleotide position 288, causing the glutamic acid (E) at amino acid position 96 to be replaced by an aspartic acid (D). 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	Pathogenic	0.81
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.076	.;T;.;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.099
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.0098	T
MetaRNN	Uncertain	0.61	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.5	N;N;.;.
REVEL	Benign	0.15
Sift	Benign	0.10	T;T;.;.
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.99	D;P;.;.
Vest4		0.72
MutPred		0.26		Loss of catalytic residue at E96 (P = 0.0979);Loss of catalytic residue at E96 (P = 0.0979);.;Loss of catalytic residue at E96 (P = 0.0979);
MVP		0.68
MPC		0.46
ClinPred		0.68	D
GERP RS		0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-170118921;