6-63646802-C-T

Variant names:

• chr6-63646802-C-T
• rs1192077289
• NM_001370348.2:c.244+7C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001370348.2(PHF3):​c.244+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 879,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 23)
  • Exomes 𝑓: 0.00021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PHF3 NM_001370348.2 splice_region, intron
• Scores: Splicing: ADA: 0.01519
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF3	NM_001370348.2	c.244+7C>T		splice_region_variant, intron_variant	Intron 2 of 15	ENST00000262043.8	NP_001357277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF3	ENST00000262043.8	c.244+7C>T		splice_region_variant, intron_variant	Intron 2 of 15	5	NM_001370348.2	ENSP00000262043.4

Frequencies

GnomAD3 genomes AF: 0.00177 AC: 135 AN: 76460 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00241

Gnomad AMI AF: 0.00508

Gnomad AMR AF: 0.00188

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00119

Gnomad SAS AF: 0.00220

Gnomad FIN AF: 0.000968

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00161

Gnomad OTH AF: 0.00193

GnomAD2 exomes AF: 0.0000738 AC: 6 AN: 81314 AF XY: 0.0000877

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000846

Gnomad NFE exome AF: 0.0000433

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000209 AC: 184 AN: 879964 Hom.: 0 Cov.: 29 AF XY: 0.000241 AC XY: 103 AN XY: 427058

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

African (AFR) AF: 0.000108 AC: 2 AN: 18544

American (AMR) AF: 0.00 AC: 0 AN: 14448

Ashkenazi Jewish (ASJ) AF: 0.000323 AC: 4 AN: 12372

East Asian (EAS) AF: 0.0000843 AC: 2 AN: 23716

South Asian (SAS) AF: 0.00214 AC: 53 AN: 24816

European-Finnish (FIN) AF: 0.000352 AC: 8 AN: 22704

Middle Eastern (MID) AF: 0.000431 AC: 1 AN: 2320

European-Non Finnish (NFE) AF: 0.000145 AC: 105 AN: 725752

Other (OTH) AF: 0.000255 AC: 9 AN: 35292

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00177 AC: 135 AN: 76456 Hom.: 0 Cov.: 23 AF XY: 0.00212 AC XY: 76 AN XY: 35794

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

African (AFR) AF: 0.00241 AC: 40 AN: 16630

American (AMR) AF: 0.00187 AC: 13 AN: 6938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2216

East Asian (EAS) AF: 0.00119 AC: 3 AN: 2518

South Asian (SAS) AF: 0.00222 AC: 5 AN: 2256

European-Finnish (FIN) AF: 0.000968 AC: 3 AN: 3100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 88

European-Non Finnish (NFE) AF: 0.00161 AC: 66 AN: 41082

Other (OTH) AF: 0.00193 AC: 2 AN: 1038

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000506 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.90
PhyloP100		2.7
PromoterAI		0.0068	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.015
dbscSNV1_RF	Benign	0.064
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: rs1192077289; hg19: chr6-64356707;