7-77840260-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000248550.7(PHTF2):c.5C>T(p.Ala2Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000688 in 1,454,214 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: PHTF2 ENST00000248550.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.07

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36904305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHTF2	NM_001395272.1	c.5C>T	p.Ala2Val	missense_variant	2/19	ENST00000422959.8
PHTF2	XM_011516422.4	c.5C>T	p.Ala2Val	missense_variant	2/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHTF2	ENST00000422959.8	c.5C>T	p.Ala2Val	missense_variant	2/19	5	NM_001395272.1	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000688 AC: 10 AN: 1454214 Hom.: 0 Cov.: 27 AF XY: 0.00000414 AC XY: 3 AN XY: 723848

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000905

Gnomad4 OTH exome AF: 0.00

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

Dec 08, 2023

The c.5C>T (p.A2V) alteration is located in exon 1 (coding exon 1) of the PHTF2 gene. This alteration results from a C to T substitution at nucleotide position 5, causing the alanine (A) at amino acid position 2 to be replaced by a valine (V). 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	Uncertain	0.50
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
Cadd	Pathogenic	28
Dann	Uncertain	1.0
DEOGEN2	Benign	0.048	T;.;.;.;.;.;.;T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.43	T;D;D;D;D;D;D;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.37	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.0	N;N;N;N;N;N;N;N
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.76	N;N;N;N;N;N;N;N
REVEL	Benign	0.18
Sift	Uncertain	0.0080	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.033	D;D;D;D;D;D;D;D
Polyphen		1.0	D;P;P;.;.;P;.;D
Vest4		0.61
MutPred		0.24		Gain of MoRF binding (P = 0.0985);Gain of MoRF binding (P = 0.0985);Gain of MoRF binding (P = 0.0985);Gain of MoRF binding (P = 0.0985);Gain of MoRF binding (P = 0.0985);Gain of MoRF binding (P = 0.0985);Gain of MoRF binding (P = 0.0985);Gain of MoRF binding (P = 0.0985);
MVP		0.24
MPC		0.46
ClinPred		0.75	D
GERP RS		3.9
Varity_R		0.12
gMVP		0.57

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

LitVar

Other links and lift over

dbSNP: rs1795766643; hg19: chr7-77469577;