7-77910381-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001366089.1(PHTF2):​c.748C>T​(p.Leu250Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,460,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PHTF2
NM_001366089.1 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.50
Variant links:
Genes affected
PHTF2 (HGNC:13411): (putative homeodomain transcription factor 2) Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.110566765).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PHTF2NM_001366089.1 linkc.748C>T p.Leu250Phe missense_variant Exon 8 of 19 NP_001353018.1
PHTF2NM_001127357.2 linkc.646C>T p.Leu216Phe missense_variant Exon 7 of 18 NP_001120829.1 Q8N3S3-2
PHTF2NM_001395272.1 linkc.646C>T p.Leu216Phe missense_variant Exon 8 of 19 NP_001382201.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PHTF2ENST00000422959.8 linkc.646C>T p.Leu216Phe missense_variant Exon 8 of 19 5 ENSP00000403042.2 Q8N3S3-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000403
AC:
1
AN:
248340
Hom.:
0
AF XY:
0.00000742
AC XY:
1
AN XY:
134690
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000887
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1460810
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
726616
show subpopulations
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:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000827
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

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.646C>T (p.L216F) alteration is located in exon 7 (coding exon 7) of the PHTF2 gene. This alteration results from a C to T substitution at nucleotide position 646, causing the leucine (L) at amino acid position 216 to be replaced by a phenylalanine (F). 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
0.080
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
19
DANN
Uncertain
0.97
DEOGEN2
Benign
0.010
T;.;.;.;.;.;.;T
Eigen
Benign
-0.027
Eigen_PC
Benign
0.18
FATHMM_MKL
Benign
0.73
D
LIST_S2
Uncertain
0.87
D;D;D;D;D;D;D;.
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.11
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.76
N;.;.;.;.;.;.;N
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-0.33
.;N;N;N;N;N;N;N
REVEL
Benign
0.072
Sift
Benign
0.61
.;T;T;T;T;T;T;T
Sift4G
Benign
0.74
T;T;T;T;T;T;T;T
Polyphen
0.87
P;B;B;.;.;B;.;P
Vest4
0.12
MutPred
0.48
Gain of helix (P = 0.0199);.;.;.;.;.;.;Gain of helix (P = 0.0199);
MVP
0.27
MPC
0.16
ClinPred
0.32
T
GERP RS
5.5
Varity_R
0.22
gMVP
0.37

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs774995655; hg19: chr7-77539698; COSMIC: COSV50323641; API