7-77908930-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000248550.7(PHTF2):c.583C>T(p.Pro195Ser) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHTF2 ENST00000248550.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.675

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.021837711).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHTF2	NM_001395272.1	c.481C>T	p.Pro161Ser	missense_variant	7/19	ENST00000422959.8
PHTF2	XM_011516422.4	c.481C>T	p.Pro161Ser	missense_variant	7/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHTF2	ENST00000422959.8	c.481C>T	p.Pro161Ser	missense_variant	7/19	5	NM_001395272.1	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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

Aug 02, 2021

The c.481C>T (p.P161S) alteration is located in exon 6 (coding exon 6) of the PHTF2 gene. This alteration results from a C to T substitution at nucleotide position 481, causing the proline (P) at amino acid position 161 to be replaced by a serine (S). 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	0.065
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	12
Dann	Benign	0.27
DEOGEN2	Benign	0.0092	T;.;.;.;.;.;.;T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.49	N
LIST_S2	Uncertain	0.87	D;D;D;D;D;D;D;.
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.022	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.34	N;.;.;.;.;.;.;N
MutationTaster	Benign	0.89	D;D;D;D;D;D;D;D
PrimateAI	Benign	0.40	T
REVEL	Benign	0.045
Sift4G	Benign	0.99	T;T;T;T;T;T;T;T
Polyphen		0.63	P;B;B;.;.;B;.;P
Vest4		0.17
MutPred		0.24		Loss of catalytic residue at P194 (P = 0.0194);.;.;.;.;.;.;Loss of catalytic residue at P194 (P = 0.0194);
MVP		0.081
MPC		0.14
ClinPred		0.061	T
GERP RS		0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.050
gMVP		0.45

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: chr7-77538247;