6-63684176-G-T

Variant names:

• chr6-63684176-G-T
• rs34188763
• NM_001370348.2:c.454G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001370348.2(PHF3):​c.454G>T​(p.Ala152Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000951 in 1,613,528 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00054 (8 hom.)
• Consequence: PHF3 NM_001370348.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.262
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031266212).
• BP6: Variant 6-63684176-G-T is Benign according to our data. Variant chr6-63684176-G-T is described in ClinVar as Benign. ClinVar VariationId is 716135.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00487 (741/152164) while in subpopulation AFR AF = 0.017 (704/41526). AF 95% confidence interval is 0.0159. There are 6 homozygotes in GnomAd4. There are 349 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF3	NM_001370348.2	MANE Select	c.454G>T	p.Ala152Ser	missense	Exon 4 of 16	NP_001357277.1	Q92576-1
	PHF3	NM_015153.4		c.454G>T	p.Ala152Ser	missense	Exon 3 of 15	NP_055968.1	Q92576-1
	PHF3	NM_001290259.2		c.190G>T	p.Ala64Ser	missense	Exon 5 of 17	NP_001277188.1	Q92576-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF3	ENST00000262043.8	TSL:5 MANE Select	c.454G>T	p.Ala152Ser	missense	Exon 4 of 16	ENSP00000262043.4	Q92576-1
	PHF3	ENST00000393387.5	TSL:1	c.454G>T	p.Ala152Ser	missense	Exon 3 of 15	ENSP00000377048.1	Q92576-1
	PHF3	ENST00000509330.5	TSL:1	c.454G>T	p.Ala152Ser	missense	Exon 4 of 4	ENSP00000422841.1	D6R9X2

Frequencies

GnomAD3 genomes AF: 0.00488 AC: 742 AN: 152048 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00481

GnomAD2 exomes AF: 0.00129 AC: 324 AN: 250746 AF XY: 0.000966

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.000956

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000882

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000543 AC: 794 AN: 1461364 Hom.: 8 Cov.: 33 AF XY: 0.000466 AC XY: 339 AN XY: 726980

African (AFR) AF: 0.0188 AC: 629 AN: 33434

American (AMR) AF: 0.000941 AC: 42 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5764

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1111788

Other (OTH) AF: 0.00132 AC: 80 AN: 60378

GnomAD4 genome AF: 0.00487 AC: 741 AN: 152164 Hom.: 6 Cov.: 32 AF XY: 0.00469 AC XY: 349 AN XY: 74408

African (AFR) AF: 0.0170 AC: 704 AN: 41526

American (AMR) AF: 0.00144 AC: 22 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67976

Other (OTH) AF: 0.00476 AC: 10 AN: 2102

Alfa AF: 0.00156 Hom.: 1

Bravo AF: 0.00534

ESP6500AA AF: 0.0170 AC: 75

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00171 AC: 208

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	PHF3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.74
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.26
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.031
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.14	T
Polyphen		0.38	B
Vest4		0.18
MVP		0.093
MPC		0.070
ClinPred		0.035	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.097
Mutation Taster		=98/2	polymorphism

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: rs34188763; hg19: chr6-64394077; COSMIC: COSV99029784;