17-28913141-G-A

Variant names:

• chr17-28913141-G-A
• rs2039997397
• NM_001033561.2:c.1430C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001033561.2(PHF12):​c.1430C>T​(p.Thr477Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHF12 NM_001033561.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.06

Genes affected

PHF12 (HGNC:20816): (PHD finger protein 12) Enables phosphatidylinositol binding activity and transcription corepressor activity. Involved in negative regulation of transcription, DNA-templated. Acts upstream of or within negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of Sin3 complex and transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20279011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF12	NM_001033561.2	c.1430C>T	p.Thr477Ile	missense_variant	Exon 9 of 15	ENST00000332830.9	NP_001028733.1
PHF12	NM_001290131.2	c.1430C>T	p.Thr477Ile	missense_variant	Exon 9 of 11		NP_001277060.1
PHF12	NM_020889.3	c.1430C>T	p.Thr477Ile	missense_variant	Exon 9 of 9		NP_065940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF12	ENST00000332830.9	c.1430C>T	p.Thr477Ile	missense_variant	Exon 9 of 15	2	NM_001033561.2	ENSP00000329933.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1430C>T (p.T477I) alteration is located in exon 9 (coding exon 9) of the PHF12 gene. This alteration results from a C to T substitution at nucleotide position 1430, causing the threonine (T) at amino acid position 477 to be replaced by an isoleucine (I). 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	0.18
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.098	T;.;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Uncertain	0.63	D
MutationAssessor	Benign	1.4	L;L;L
PhyloP100		5.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.53	N;.;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.012	D;.;D
Sift4G	Benign	0.25	T;D;D
Polyphen		0.15	B;.;B
Vest4		0.23
MutPred		0.15		Loss of glycosylation at T477 (P = 0.0044);Loss of glycosylation at T477 (P = 0.0044);Loss of glycosylation at T477 (P = 0.0044);
MVP		0.28
MPC		0.28
ClinPred		0.66	D
GERP RS		4.8
PromoterAI		-0.050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.26

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

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Other links and lift over

dbSNP: rs2039997397; hg19: chr17-27240159;