7-77901866-C-G

Variant summary

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

The ENST00000248550.7(PHTF2):c.391C>G(p.Gln131Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PHTF2 ENST00000248550.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

Genes affected

PHTF2 (HGNC:13411): (putative homeodomain transcription factor 2) Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHTF2	NM_001395272.1	c.289C>G	p.Gln97Glu	missense_variant	6/19	ENST00000422959.8
PHTF2	XM_011516422.4	c.289C>G	p.Gln97Glu	missense_variant	6/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHTF2	ENST00000422959.8	c.289C>G	p.Gln97Glu	missense_variant	6/19	5	NM_001395272.1	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 13, 2023

The c.289C>G (p.Q97E) alteration is located in exon 5 (coding exon 5) of the PHTF2 gene. This alteration results from a C to G substitution at nucleotide position 289, causing the glutamine (Q) at amino acid position 97 to be replaced by a glutamic acid (E). 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	0.20
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.073	T;.;.;.;.;.;.;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;.
M_CAP	Benign	0.0065	T
MetaRNN	Uncertain	0.54	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.5	M;.;.;.;.;.;.;M
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.51	T
REVEL	Uncertain	0.31
Sift4G	Uncertain	0.053	T;T;T;D;D;T;D;T
Polyphen		0.67	P;B;P;.;.;P;.;P
Vest4		0.72
MutPred		0.54		Loss of MoRF binding (P = 0.0334);.;.;.;.;.;.;Loss of MoRF binding (P = 0.0334);
MVP		0.27
MPC		0.36
ClinPred		0.97	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.71

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: chr7-77531183;