Genetic Variant PHTF2:p.Leu216Ile (chr7-77910381-C-A) – 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>A(p.Leu216Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,460,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L216F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

PHTF2
NM_001395272.1 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

Genome browser will be placed here

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=0.11723119).

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>A	p.Leu216Ile	missense	Exon 8 of 19	NP_001382201.1	Q8N3S3-2
PHTF2	NM_001366089.1		c.748C>A	p.Leu250Ile	missense	Exon 8 of 19	NP_001353018.1	Q8N3S3-1
PHTF2	NM_001127357.2		c.646C>A	p.Leu216Ile	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>A	p.Leu216Ile	missense	Exon 8 of 19	ENSP00000403042.2	Q8N3S3-2
PHTF2	ENST00000248550.7	TSL:1	c.748C>A	p.Leu250Ile	missense	Exon 8 of 19	ENSP00000248550.7	Q8N3S3-1
PHTF2	ENST00000307305.12	TSL:1	c.634C>A	p.Leu212Ile	missense	Exon 7 of 18	ENSP00000307699.8	Q8N3S3-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1460810

Hom.:

Cov.:

AF XY:

0.00000826

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:

0.0000108

AC:

AN:

1111538

Other (OTH)

AF:

0.00

AC:

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.010

Eigen

Benign

-0.12

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.00083

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

PhyloP100

4.5

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.090

REVEL

Benign

0.058

Sift

Benign

0.43

Sift4G

Benign

0.53

Polyphen

0.0020

Vest4

0.16

MutPred

0.47

Gain of catalytic residue at L250 (P = 0.0373)

MVP

0.18

MPC

0.16

ClinPred

0.79

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.32

gMVP

0.31

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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