Genetic Variant PHYHIPL:c.*2183A>G (chr10-59247774-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000373878.3(PHYHIPL):c.*2183A>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 1,585,548 control chromosomes in the GnomAD database, including 542,358 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.75 ( 45235 hom., cov: 32)

Exomes 𝑓: 0.83 ( 497123 hom. )

Consequence

PHYHIPL
ENST00000373878.3 splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.56

Publications

9 publications found

Variant links:

Genes affected

PHYHIPL (HGNC:29378): (phytanoyl-CoA 2-hydroxylase interacting protein like) Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PHYHIPL links:

FAM13C (HGNC:19371): (family with sequence similarity 13 member C)

FAM13C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM13C	NM_198215.4 link	c.1635-37T>C		intron_variant	Intron 13 of 13	ENST00000618804.5	NP_937858.2
PHYHIPL	NM_032439.4 link	c.*2183A>G		downstream_gene_variant		ENST00000373880.9	NP_115815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM13C	ENST00000618804.5 link	c.1635-37T>C		intron_variant	Intron 13 of 13	1	NM_198215.4	ENSP00000481854.1
PHYHIPL	ENST00000373880.9 link	c.*2183A>G		downstream_gene_variant		1	NM_032439.4	ENSP00000362987.4

Frequencies

GnomAD3 genomes

AF:

0.755

AC:

114657

AN:

151926

Hom.:

45227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.507

Gnomad AMI

AF:

0.881

Gnomad AMR

AF:

0.853

Gnomad ASJ

AF:

0.814

Gnomad EAS

AF:

0.896

Gnomad SAS

AF:

0.720

Gnomad FIN

AF:

0.895

Gnomad MID

AF:

0.832

Gnomad NFE

AF:

0.847

Gnomad OTH

AF:

0.789

GnomAD2 exomes

AF:

0.820

AC:

197626

AN:

241036

AF XY:

0.820

show subpopulations

Gnomad AFR exome

AF:

0.499

Gnomad AMR exome

AF:

0.868

Gnomad ASJ exome

AF:

0.827

Gnomad EAS exome

AF:

0.913

Gnomad FIN exome

AF:

0.895

Gnomad NFE exome

AF:

0.846

Gnomad OTH exome

AF:

0.832

GnomAD4 exome

AF:

0.830

AC:

1189762

AN:

1433504

Hom.:

497123

Cov.:

AF XY:

0.828

AC XY:

589388

AN XY:

712000

show subpopulations

African (AFR)

AF:

0.490

AC:

15852

AN:

32360

American (AMR)

AF:

0.869

AC:

37046

AN:

42652

Ashkenazi Jewish (ASJ)

AF:

0.828

AC:

21310

AN:

25752

East Asian (EAS)

AF:

0.851

AC:

33307

AN:

39144

South Asian (SAS)

AF:

0.720

AC:

59893

AN:

83184

European-Finnish (FIN)

AF:

0.896

AC:

46274

AN:

51640

Middle Eastern (MID)

AF:

0.791

AC:

4502

AN:

5692

European-Non Finnish (NFE)

AF:

0.844

AC:

923194

AN:

1093698

Other (OTH)

AF:

0.815

AC:

48384

AN:

59382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

8117

16235

24352

32470

40587

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20776

41552

62328

83104

103880

<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:

0.754

AC:

114696

AN:

152044

Hom.:

45235

Cov.:

AF XY:

0.759

AC XY:

56443

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.506

AC:

20971

AN:

41420

American (AMR)

AF:

0.854

AC:

13045

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.814

AC:

2823

AN:

3470

East Asian (EAS)

AF:

0.896

AC:

4640

AN:

5178

South Asian (SAS)

AF:

0.720

AC:

3469

AN:

4820

European-Finnish (FIN)

AF:

0.895

AC:

9497

AN:

10606

Middle Eastern (MID)

AF:

0.833

AC:

245

AN:

294

European-Non Finnish (NFE)

AF:

0.847

AC:

57540

AN:

67950

Other (OTH)

AF:

0.788

AC:

1664

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1247

2493

3740

4986

6233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

838

1676

2514

3352

4190

<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:

0.814

Hom.:

165847

Bravo

AF:

0.741

Asia WGS

AF:

0.776

AC:

2696

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.4

(source)

DANN

Benign

0.72

PhyloP100

1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over