rs764819983

Variant names:

• chr6-33415017-C-T
• rs764819983
• NM_024165.3:c.1112C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33415017-C-T
• chr6-33415017-C-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_024165.3(PHF1):​c.1112C>T​(p.Pro371Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,572,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: PHF1 NM_024165.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.26
• Publications: 0 publications found

Genes affected

PHF1 (HGNC:8919): (PHD finger protein 1) This gene encodes a Polycomb group protein. The protein is a component of a histone H3 lysine-27 (H3K27)-specific methyltransferase complex, and functions in transcriptional repression of homeotic genes. The protein is also recruited to double-strand breaks, and reduced protein levels results in X-ray sensitivity and increased homologous recombination. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.031372786).
• BS2: High AC in GnomAdExome4 at 36 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024165.3. 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
	PHF1	NM_024165.3	MANE Select	c.1112C>T	p.Pro371Leu	missense	Exon 12 of 15	NP_077084.2	O43189-1
	PHF1	NM_002636.5		c.1101C>T	p.Ala367Ala	synonymous	Exon 12 of 14	NP_002627.2	O43189-2
	PHF1	NR_027692.2		n.1319C>T		non_coding_transcript_exon	Exon 12 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF1	ENST00000374516.8	TSL:1 MANE Select	c.1112C>T	p.Pro371Leu	missense	Exon 12 of 15	ENSP00000363640.3	O43189-1
	PHF1	ENST00000374512.7	TSL:1	c.1101C>T	p.Ala367Ala	synonymous	Exon 12 of 14	ENSP00000363636.3	O43189-2
	PHF1	ENST00000859011.1		c.1130C>T	p.Pro377Leu	missense	Exon 12 of 15	ENSP00000529070.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151920 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000165 AC: 3 AN: 181640 AF XY: 0.0000102

Gnomad AFR exome AF: 0.0000939

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000270

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000253 AC: 36 AN: 1420358 Hom.: 0 Cov.: 38 AF XY: 0.0000270 AC XY: 19 AN XY: 703412

African (AFR) AF: 0.0000311 AC: 1 AN: 32138

American (AMR) AF: 0.0000266 AC: 1 AN: 37534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25418

East Asian (EAS) AF: 0.00 AC: 0 AN: 36806

South Asian (SAS) AF: 0.00 AC: 0 AN: 82672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4984

European-Non Finnish (NFE) AF: 0.0000293 AC: 32 AN: 1091376

Other (OTH) AF: 0.0000340 AC: 2 AN: 58766

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151920 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74204

African (AFR) AF: 0.0000726 AC: 3 AN: 41328

American (AMR) AF: 0.00 AC: 0 AN: 15260

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67946

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.85
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.3
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.034
Sift	Benign	0.72	T
Sift4G	Benign	0.19	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.25		Loss of glycosylation at P371 (P = 0.0072)
MVP		0.19
MPC		1.1
ClinPred		0.078	T
GERP RS		0.99
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.033
gMVP		0.46
Mutation Taster		=94/6	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: rs764819983; hg19: chr6-33382794;