Genetic Variant PHTF2:p.Leu216Phe (chr7-77910381-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001395272.1(PHTF2):c.646C>T(p.Leu216Phe) 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. 13/21 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_001395272.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.50

Publications

1 publications found

Variant links:

Genes affected

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

PHTF2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.110566765).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395272.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHTF2	NM_001395272.1	MANE Select	c.646C>T	p.Leu216Phe	missense	Exon 8 of 19	NP_001382201.1	Q8N3S3-2
PHTF2	NM_001366089.1		c.748C>T	p.Leu250Phe	missense	Exon 8 of 19	NP_001353018.1	Q8N3S3-1
PHTF2	NM_001127357.2		c.646C>T	p.Leu216Phe	missense	Exon 7 of 18	NP_001120829.1	Q8N3S3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHTF2	ENST00000422959.8	TSL:5 MANE Select	c.646C>T	p.Leu216Phe	missense	Exon 8 of 19	ENSP00000403042.2	Q8N3S3-2
PHTF2	ENST00000248550.7	TSL:1	c.748C>T	p.Leu250Phe	missense	Exon 8 of 19	ENSP00000248550.7	Q8N3S3-1
PHTF2	ENST00000307305.12	TSL:1	c.634C>T	p.Leu212Phe	missense	Exon 7 of 18	ENSP00000307699.8	Q8N3S3-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248340

AF XY:

0.00000742

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460810

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726616

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.00

AC:

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

85984

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111538

Other (OTH)

AF:

0.00

AC:

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000827

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.010

Eigen

Benign

-0.027

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0012

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.76

PhyloP100

4.5

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.33

REVEL

Benign

0.072

Sift

Benign

0.61

Sift4G

Benign

0.74

Polyphen

0.87

Vest4

0.12

MutPred

0.48

Gain of helix (P = 0.0199)

MVP

0.27

MPC

0.16

ClinPred

0.32

GERP RS

5.5

Varity_R

0.22

gMVP

0.37

Mutation Taster

=77/23

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over