Variant 1-113699769-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001323043.2(PHTF1):c.2077C>T(p.Pro693Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000498 in 1,405,148 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000040 ( 0 hom. )

Consequence

PHTF1
NM_001323043.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.96

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHTF1	NM_001323043.2 linkuse as main transcript	c.2077C>T	p.Pro693Ser	missense_variant	17/19	ENST00000369604.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHTF1	ENST00000369604.6 linkuse as main transcript	c.2077C>T	p.Pro693Ser	missense_variant	17/19	5	NM_001323043.2	P1	Q9UMS5-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000399

AC:

AN:

1253188

Hom.:

Cov.:

AF XY:

0.00000637

AC XY:

AN XY:

628230

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:

0.00000532

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151960

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000389

Hom.:

Bravo

AF:

0.0000151

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

Oct 26, 2022

The c.2077C>T (p.P693S) alteration is located in exon 16 (coding exon 16) of the PHTF1 gene. This alteration results from a C to T substitution at nucleotide position 2077, causing the proline (P) at amino acid position 693 to be replaced by a serine (S). 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

0.99

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Uncertain

0.57

D;.;.;D

Eigen

Pathogenic

0.99

Eigen_PC

Pathogenic

0.99

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D;.

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.58

D;D;D;D

MetaSVM

Uncertain

-0.12

MutationAssessor

Uncertain

2.3

M;.;.;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-6.8

D;D;D;D

REVEL

Uncertain

0.54

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;.;.;D

Vest4

0.72

MutPred

0.26

Loss of glycosylation at P693 (P = 0.0433);.;.;Loss of glycosylation at P693 (P = 0.0433);

MVP

0.39

MPC

0.64

ClinPred

1.0

GERP RS

6.2

Varity_R

0.84

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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