17-28906947-C-T

Variant names:

• chr17-28906947-C-T
• NM_001033561.2:c.2589G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001033561.2(PHF12):​c.2589G>A​(p.Thr863Thr) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHF12 NM_001033561.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.420
• Publications: 0 publications found

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]

PHF12 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: G2P

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 17-28906947-C-T is Benign according to our data. Variant chr17-28906947-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2647605.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.42 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033561.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF12	NM_001033561.2	MANE Select	c.2589G>A	p.Thr863Thr	synonymous	Exon 14 of 15	NP_001028733.1	Q96QT6-1
	PHF12	NM_001290131.2		c.*3088G>A		3_prime_UTR	Exon 11 of 11	NP_001277060.1	Q96QT6-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF12	ENST00000332830.9	TSL:2 MANE Select	c.2589G>A	p.Thr863Thr	synonymous	Exon 14 of 15	ENSP00000329933.4	Q96QT6-1
	PHF12	ENST00000577226.5	TSL:1	c.*3088G>A		3_prime_UTR	Exon 11 of 11	ENSP00000465161.1	Q96QT6-5
	PHF12	ENST00000930975.1		c.2628G>A	p.Thr876Thr	synonymous	Exon 15 of 16	ENSP00000601034.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		-0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr17-27233965;