chr6-63687952-A-C

Variant names:

• chr6-63687952-A-C
• rs10755432
• NM_001370348.2:c.2189+2041A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370348.2(PHF3):​c.2189+2041A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,814 control chromosomes in the GnomAD database, including 24,476 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (24476 hom., cov: 30)
• Consequence: PHF3 NM_001370348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• Publications: 2 publications found

Genes affected

PHF3 (HGNC:8921): (PHD finger protein 3) This gene encodes a member of a PHD finger-containing gene family. This gene may function as a transcription factor and may be involved in glioblastomas development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370348.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF3	NM_001370348.2	MANE Select	c.2189+2041A>C		intron	N/A	NP_001357277.1
	PHF3	NM_015153.4		c.2189+2041A>C		intron	N/A	NP_055968.1
	PHF3	NM_001290259.2		c.1925+2041A>C		intron	N/A	NP_001277188.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF3	ENST00000262043.8	TSL:5 MANE Select	c.2189+2041A>C		intron	N/A	ENSP00000262043.4
	PHF3	ENST00000393387.5	TSL:1	c.2189+2041A>C		intron	N/A	ENSP00000377048.1
	PHF3	ENST00000506783.5	TSL:1	c.1631+2041A>C		intron	N/A	ENSP00000424694.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83175 AN: 151694 Hom.: 24423 Cov.: 30

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.511

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.549 AC: 83287 AN: 151814 Hom.: 24476 Cov.: 30 AF XY: 0.546 AC XY: 40534 AN XY: 74190

African (AFR) AF: 0.766 AC: 31717 AN: 41410

American (AMR) AF: 0.562 AC: 8577 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1638 AN: 3464

East Asian (EAS) AF: 0.449 AC: 2296 AN: 5116

South Asian (SAS) AF: 0.564 AC: 2710 AN: 4804

European-Finnish (FIN) AF: 0.359 AC: 3787 AN: 10548

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30902 AN: 67896

Other (OTH) AF: 0.507 AC: 1069 AN: 2108

Alfa AF: 0.518 Hom.: 3581

Bravo AF: 0.573

Asia WGS AF: 0.481 AC: 1672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.3
DANN	Benign	0.62
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10755432; hg19: chr6-64397853;