6-33412282-C-A

Variant names:

• chr6-33412282-C-A
• NM_024165.3:c.19C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024165.3(PHF1):​c.19C>A​(p.Leu7Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHF1 NM_024165.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19313961).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF1	NM_024165.3	c.19C>A	p.Leu7Met	missense_variant	Exon 2 of 15	ENST00000374516.8	NP_077084.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF1	ENST00000374516.8	c.19C>A	p.Leu7Met	missense_variant	Exon 2 of 15	1	NM_024165.3	ENSP00000363640.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.19C>A (p.L7M) alteration is located in exon 2 (coding exon 1) of the PHF1 gene. This alteration results from a C to A substitution at nucleotide position 19, causing the leucine (L) at amino acid position 7 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	.;.;.;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.84	T;T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;.;N;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.28	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.069	T;T;D;D
Sift4G	Benign	0.064	T;T;D;D
Polyphen		1.0, 0.98	.;.;D;D
Vest4		0.33, 0.26
MutPred		0.097		Gain of MoRF binding (P = 0.0648);Gain of MoRF binding (P = 0.0648);Gain of MoRF binding (P = 0.0648);Gain of MoRF binding (P = 0.0648);
MVP		0.24
MPC		0.87
ClinPred		0.79	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.52
gMVP		0.19

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-33380059;