dbSNP rs559299935: PHTF2:p.Ser320Cys (chr7-77922720-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001395272.1(PHTF2):c.959C>G(p.Ser320Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,608,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

PHTF2
NM_001395272.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026533365).

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.959C>G	p.Ser320Cys	missense	Exon 10 of 19	NP_001382201.1	Q8N3S3-2
PHTF2	NM_001366089.1		c.1061C>G	p.Ser354Cys	missense	Exon 10 of 19	NP_001353018.1	Q8N3S3-1
PHTF2	NM_001127357.2		c.959C>G	p.Ser320Cys	missense	Exon 9 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.959C>G	p.Ser320Cys	missense	Exon 10 of 19	ENSP00000403042.2	Q8N3S3-2
PHTF2	ENST00000248550.7	TSL:1	c.1061C>G	p.Ser354Cys	missense	Exon 10 of 19	ENSP00000248550.7	Q8N3S3-1
PHTF2	ENST00000307305.12	TSL:1	c.947C>G	p.Ser316Cys	missense	Exon 9 of 18	ENSP00000307699.8	Q8N3S3-3

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000456

AC:

AN:

241310

AF XY:

0.0000383

show subpopulations

Gnomad AFR exome

AF:

0.000613

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000165

AC:

AN:

1456674

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

724156

show subpopulations

African (AFR)

AF:

0.000539

AC:

AN:

33410

American (AMR)

AF:

0.0000227

AC:

AN:

44150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25914

East Asian (EAS)

AF:

0.00

AC:

AN:

39590

South Asian (SAS)

AF:

0.00

AC:

AN:

85288

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53168

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109216

Other (OTH)

AF:

0.0000831

AC:

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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

AF:

0.000131

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000457

AC:

AN:

41578

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.000136

ExAC

AF:

0.0000497

AC:

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

0.078

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.044

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0032

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

2.3

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.6

REVEL

Benign

0.032

Sift

Benign

0.11

Sift4G

Benign

0.076

Polyphen

0.0010

Vest4

0.47

MVP

0.23

MPC

0.14

ClinPred

0.016

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.090

gMVP

0.55

Mutation Taster

=89/11

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over