6-63646806-CTTTTTTTTTTTTTT-CTTTTTTTTTTTTT

Variant names:

• chr6-63646806-CT-C
• rs11285703
• NM_001370348.2:c.244+33delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001370348.2(PHF3):​c.244+33delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (8513 hom., cov: 0)
  • Exomes 𝑓: 0.34 (677 hom.)
  • Failed GnomAD Quality Control
• Consequence: PHF3 NM_001370348.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.19
• Publications: 1 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 -10 ACMG points.

• BP6: Variant 6-63646806-CT-C is Benign according to our data. Variant chr6-63646806-CT-C is described in ClinVar as Benign. ClinVar VariationId is 2776132.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.561 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF3	NM_001370348.2	MANE Select	c.244+33delT		intron	N/A	NP_001357277.1	Q92576-1
	PHF3	NM_015153.4		c.244+33delT		intron	N/A	NP_055968.1	Q92576-1
	PHF3	NM_001290259.2		c.-214+33delT		intron	N/A	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.244+12delT		intron	N/A	ENSP00000262043.4	Q92576-1
	PHF3	ENST00000393387.5	TSL:1	c.244+12delT		intron	N/A	ENSP00000377048.1	Q92576-1
	PHF3	ENST00000506783.5	TSL:1	c.-153+10657delT		intron	N/A	ENSP00000424694.1	E7EVH3

Frequencies

GnomAD3 genomes AF: 0.484 AC: 41136 AN: 85066 Hom.: 8505 Cov.: 0

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.438

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.432

GnomAD2 exomes AF: 0.00337 AC: 88 AN: 26084 AF XY: 0.00213

Gnomad AFR exome AF: 0.00445

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.0150

Gnomad EAS exome AF: 0.00269

Gnomad FIN exome AF: 0.00712

Gnomad NFE exome AF: 0.00300

Gnomad OTH exome AF: 0.00415

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.343 AC: 313748 AN: 914414 Hom.: 677 Cov.: 0 AF XY: 0.341 AC XY: 148744 AN XY: 435712

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.361 AC: 6846 AN: 18980

American (AMR) AF: 0.242 AC: 2358 AN: 9744

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 3945 AN: 11872

East Asian (EAS) AF: 0.308 AC: 7010 AN: 22728

South Asian (SAS) AF: 0.329 AC: 6046 AN: 18404

European-Finnish (FIN) AF: 0.283 AC: 5406 AN: 19092

Middle Eastern (MID) AF: 0.356 AC: 852 AN: 2396

European-Non Finnish (NFE) AF: 0.347 AC: 268969 AN: 774896

Other (OTH) AF: 0.339 AC: 12316 AN: 36302

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.484 AC: 41129 AN: 85048 Hom.: 8513 Cov.: 0 AF XY: 0.479 AC XY: 18734 AN XY: 39150

African (AFR) AF: 0.569 AC: 12212 AN: 21458

American (AMR) AF: 0.505 AC: 4068 AN: 8060

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1095 AN: 2378

East Asian (EAS) AF: 0.451 AC: 1337 AN: 2964

South Asian (SAS) AF: 0.538 AC: 1238 AN: 2302

European-Finnish (FIN) AF: 0.304 AC: 831 AN: 2732

Middle Eastern (MID) AF: 0.449 AC: 53 AN: 118

European-Non Finnish (NFE) AF: 0.450 AC: 19500 AN: 43290

Other (OTH) AF: 0.429 AC: 475 AN: 1106

Alfa AF: 0.163 Hom.: 238

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
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: rs11285703; hg19: chr6-64356711;