Genetic Variant ENST00000248550.7:c.379C>A (chr7-77901854-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000248550.7(PHTF2):c.379C>A(p.Arg127Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,601,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

PHTF2
ENST00000248550.7 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.94

Publications

3 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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000248550.7. 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.277C>A	p.Arg93Arg	synonymous	Exon 6 of 19	NP_001382201.1	Q8N3S3-2
PHTF2	NM_001366089.1		c.379C>A	p.Arg127Arg	synonymous	Exon 6 of 19	NP_001353018.1	Q8N3S3-1
PHTF2	NM_001127357.2		c.277C>A	p.Arg93Arg	synonymous	Exon 5 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.277C>A	p.Arg93Arg	synonymous	Exon 6 of 19	ENSP00000403042.2	Q8N3S3-2
PHTF2	ENST00000248550.7	TSL:1	c.379C>A	p.Arg127Arg	synonymous	Exon 6 of 19	ENSP00000248550.7	Q8N3S3-1
PHTF2	ENST00000307305.12	TSL:1	c.265C>A	p.Arg89Arg	synonymous	Exon 5 of 18	ENSP00000307699.8	Q8N3S3-3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152054

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:

0.00

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

GnomAD2 exomes

AF:

0.00000835

AC:

AN:

239512

AF XY:

0.0000154

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:

0.00000920

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000166

AC:

AN:

1449260

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

720610

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33188

American (AMR)

AF:

0.00

AC:

AN:

43572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25854

East Asian (EAS)

AF:

0.00

AC:

AN:

39272

South Asian (SAS)

AF:

0.0000119

AC:

AN:

84160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.0000199

AC:

AN:

1104548

Other (OTH)

AF:

0.0000167

AC:

AN:

59890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

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:

0.00000658

AC:

AN:

152054

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41406

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: 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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over