17-28906876-G-C

Position:

• chr17-28906876-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_001033561.2(PHF12):​c.2660C>G​(p.Ala887Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,336 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PHF12 NM_001033561.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.86

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

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34929729).
• BP6: Variant 17-28906876-G-C is Benign according to our data. Variant chr17-28906876-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1343180.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF12	NM_001033561.2	c.2660C>G	p.Ala887Gly	missense_variant	14/15	ENST00000332830.9	NP_001028733.1
PHF12	NM_001290131.2	c.*3159C>G		3_prime_UTR_variant	11/11		NP_001277060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF12	ENST00000332830.9	c.2660C>G	p.Ala887Gly	missense_variant	14/15	2	NM_001033561.2	ENSP00000329933.4
PHF12	ENST00000577226	c.*3159C>G		3_prime_UTR_variant	11/11	1		ENSP00000465161.1
PHF12	ENST00000589176.1	n.*195C>G		non_coding_transcript_exon_variant	5/6	5		ENSP00000465255.1
PHF12	ENST00000589176.1	n.*195C>G		3_prime_UTR_variant	5/6	5		ENSP00000465255.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455336 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723842

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine

Mar 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	0.73	D
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.51
Sift	Benign	0.15	T
Sift4G	Benign	0.17	T
Polyphen		0.98	D
Vest4		0.34
MutPred		0.21		Loss of helix (P = 0.0167);
MVP		0.57
MPC		0.42
ClinPred		0.84	D
GERP RS		5.0
Varity_R		0.26
gMVP		0.30

Splicing

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: chr17-27233894;