6-63684165-A-G

Variant names:

• chr6-63684165-A-G
• rs41271581
• NM_001370348.2:c.443A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001370348.2(PHF3):​c.443A>G​(p.Lys148Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00866 in 1,612,520 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0085 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0087 (90 hom.)
• Consequence: PHF3 NM_001370348.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.43
• Publications: 13 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0066666007).
• BP6: Variant 6-63684165-A-G is Benign according to our data. Variant chr6-63684165-A-G is described in ClinVar as Benign. ClinVar VariationId is 781871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 10 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.443A>G	p.Lys148Arg	missense	Exon 4 of 16	NP_001357277.1	Q92576-1
	PHF3	NM_015153.4		c.443A>G	p.Lys148Arg	missense	Exon 3 of 15	NP_055968.1	Q92576-1
	PHF3	NM_001290259.2		c.179A>G	p.Lys60Arg	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.443A>G	p.Lys148Arg	missense	Exon 4 of 16	ENSP00000262043.4	Q92576-1
	PHF3	ENST00000393387.5	TSL:1	c.443A>G	p.Lys148Arg	missense	Exon 3 of 15	ENSP00000377048.1	Q92576-1
	PHF3	ENST00000509330.5	TSL:1	c.443A>G	p.Lys148Arg	missense	Exon 4 of 4	ENSP00000422841.1	D6R9X2

Frequencies

GnomAD3 genomes AF: 0.00845 AC: 1286 AN: 152152 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0338

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00941

Gnomad OTH AF: 0.00959

GnomAD2 exomes AF: 0.00951 AC: 2374 AN: 249728 AF XY: 0.00930

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00324

Gnomad ASJ exome AF: 0.0382

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0311

Gnomad NFE exome AF: 0.00875

Gnomad OTH exome AF: 0.00973

GnomAD4 exome AF: 0.00868 AC: 12675 AN: 1460250 Hom.: 90 Cov.: 32 AF XY: 0.00867 AC XY: 6297 AN XY: 726392

African (AFR) AF: 0.00168 AC: 56 AN: 33348

American (AMR) AF: 0.00327 AC: 145 AN: 44410

Ashkenazi Jewish (ASJ) AF: 0.0364 AC: 946 AN: 26008

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

South Asian (SAS) AF: 0.00448 AC: 385 AN: 85930

European-Finnish (FIN) AF: 0.0305 AC: 1630 AN: 53360

Middle Eastern (MID) AF: 0.0158 AC: 91 AN: 5754

European-Non Finnish (NFE) AF: 0.00789 AC: 8766 AN: 1111436

Other (OTH) AF: 0.0109 AC: 656 AN: 60318

GnomAD4 genome AF: 0.00845 AC: 1287 AN: 152270 Hom.: 10 Cov.: 32 AF XY: 0.00925 AC XY: 689 AN XY: 74472

African (AFR) AF: 0.00190 AC: 79 AN: 41564

American (AMR) AF: 0.00288 AC: 44 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3470

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

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4828

European-Finnish (FIN) AF: 0.0338 AC: 359 AN: 10608

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00941 AC: 640 AN: 68000

Other (OTH) AF: 0.00949 AC: 20 AN: 2108

Alfa AF: 0.00873 Hom.: 27

Bravo AF: 0.00538

TwinsUK AF: 0.00944 AC: 35

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00942 AC: 81

ExAC AF: 0.00932 AC: 1132

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00797

EpiControl AF: 0.00889

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.86	D
MetaRNN	Benign	0.0067	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.55	N
PhyloP100		4.4
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.047	D
Polyphen		1.0	D
Vest4		0.46
MVP		0.56
MPC		0.30
ClinPred		0.036	T
GERP RS		5.9
Varity_R		0.33
gMVP		0.18
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs41271581; hg19: chr6-64394066; COSMIC: COSV100014299;