Variant 1-113706118-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001323043.2(PHTF1):c.1443T>A(p.Asn481Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

PHTF1
NM_001323043.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.224

Variant links:

Genes affected

PHTF1 (HGNC:8939): (putative homeodomain transcription factor 1) Predicted to be located in cis-Golgi network and endoplasmic reticulum membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PHTF1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHTF1	NM_001323043.2 linkuse as main transcript	c.1443T>A	p.Asn481Lys	missense_variant	13/19	ENST00000369604.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHTF1	ENST00000369604.6 linkuse as main transcript	c.1443T>A	p.Asn481Lys	missense_variant	13/19	5	NM_001323043.2	P1	Q9UMS5-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250782

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135504

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.1443T>A (p.N481K) alteration is located in exon 12 (coding exon 12) of the PHTF1 gene. This alteration results from a T to A substitution at nucleotide position 1443, causing the asparagine (N) at amino acid position 481 to be replaced by a lysine (K). 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

Pathogenic

0.68

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

Cadd

Benign

Dann

Benign

0.95

DEOGEN2

Benign

0.056

T;.;.;T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.82

T;T;T;.;T

M_CAP

Benign

0.0084

MetaRNN

Pathogenic

0.80

D;D;D;D;D

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;.;.;L;L

MutationTaster

Benign

1.0

D;N;N;N;N;N;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.2

N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.35

T;T;T;T;D

Sift4G

Benign

0.65

T;T;T;T;T

Polyphen

0.0080

B;.;.;B;B

Vest4

0.75

MutPred

0.82

Gain of ubiquitination at N481 (P = 0.0289);.;.;Gain of ubiquitination at N481 (P = 0.0289);Gain of ubiquitination at N481 (P = 0.0289);

MVP

0.12

MPC

0.17

ClinPred

0.18

GERP RS

-2.0

Varity_R

0.090

gMVP

0.79

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over