NM_001370348.2:c.-25-2785A>G

Variant names:

• chr6-63643742-A-G
• rs3757350
• NM_001370348.2:c.-25-2785A>G

Variant summary

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

The NM_001370348.2(PHF3):​c.-25-2785A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0782 in 152,284 control chromosomes in the GnomAD database, including 537 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 0.078 (537 hom., cov: 32)
• Consequence: PHF3 NM_001370348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.622
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF3	NM_001370348.2	c.-25-2785A>G		intron_variant	Intron 1 of 15	ENST00000262043.8	NP_001357277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF3	ENST00000262043.8	c.-25-2785A>G		intron_variant	Intron 1 of 15	5	NM_001370348.2	ENSP00000262043.4

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11884 AN: 152166 Hom.: 535 Cov.: 32

Gnomad AFR AF: 0.0485

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0946

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.0679

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0812

Gnomad OTH AF: 0.0607

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

GnomAD4 genome AF: 0.0781 AC: 11901 AN: 152284 Hom.: 537 Cov.: 32 AF XY: 0.0809 AC XY: 6024 AN XY: 74456

African (AFR) AF: 0.0486 AC: 2019 AN: 41562

American (AMR) AF: 0.0951 AC: 1455 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 201 AN: 3472

East Asian (EAS) AF: 0.164 AC: 852 AN: 5184

South Asian (SAS) AF: 0.0679 AC: 328 AN: 4828

European-Finnish (FIN) AF: 0.123 AC: 1299 AN: 10602

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0812 AC: 5522 AN: 68016

Other (OTH) AF: 0.0591 AC: 125 AN: 2114

Alfa AF: 0.0772 Hom.: 825

Bravo AF: 0.0771

Asia WGS AF: 0.0930 AC: 325 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.1
DANN	Benign	0.59
PhyloP100		0.62
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: rs3757350; hg19: chr6-64353647;