Genetic Variant C14orf39:c.-144+6534T>G (chr14-60508861-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000556799.1(C14orf39):c.-144+6534T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 160,092 control chromosomes in the GnomAD database, including 61,871 homozygotes. 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 0.87 ( 58060 hom., cov: 26)

Exomes 𝑓: 0.92 ( 3811 hom. )

Consequence

C14orf39
ENST00000556799.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.717

Publications

6 publications found

Variant links:

Genes affected

C14orf39 (HGNC:19849): (chromosome 14 open reading frame 39) Predicted to be involved in gamete generation and meiosis I. Predicted to be located in chromosome. Predicted to be active in central element. Implicated in primary ovarian insufficiency 18 and spermatogenic failure 52. [provided by Alliance of Genome Resources, Apr 2022]

C14orf39 Gene-Disease associations (from GenCC):

premature ovarian failure 18
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
spermatogenic failure 52
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

C14orf39 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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C14orf39	XM_047431324.1 link	c.-144+6534T>G		intron_variant	Intron 1 of 18		XP_047287280.1
C14orf39	XM_017021250.3 link	c.-9570T>G		upstream_gene_variant			XP_016876739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C14orf39	ENST00000556799.1 link	c.-144+6534T>G		intron_variant	Intron 1 of 5	4		ENSP00000451441.1

Frequencies

GnomAD3 genomes

AF:

0.874

AC:

131864

AN:

150890

Hom.:

58002

Cov.:

show subpopulations

Gnomad AFR

AF:

0.767

Gnomad AMI

AF:

0.946

Gnomad AMR

AF:

0.907

Gnomad ASJ

AF:

0.901

Gnomad EAS

AF:

0.881

Gnomad SAS

AF:

0.753

Gnomad FIN

AF:

0.975

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.921

Gnomad OTH

AF:

0.872

GnomAD4 exome

AF:

0.916

AC:

8306

AN:

9072

Hom.:

3811

AF XY:

0.907

AC XY:

3866

AN XY:

4262

show subpopulations

African (AFR)

AF:

0.763

AC:

AN:

American (AMR)

AF:

0.917

AC:

376

AN:

410

Ashkenazi Jewish (ASJ)

AF:

0.882

AC:

120

AN:

136

East Asian (EAS)

AF:

0.850

AC:

AN:

South Asian (SAS)

AF:

0.754

AC:

401

AN:

532

European-Finnish (FIN)

AF:

0.947

AC:

305

AN:

322

Middle Eastern (MID)

AF:

0.917

AC:

AN:

European-Non Finnish (NFE)

AF:

0.927

AC:

6460

AN:

6966

Other (OTH)

AF:

0.928

AC:

531

AN:

572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

128

160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.874

AC:

131987

AN:

151020

Hom.:

58060

Cov.:

AF XY:

0.875

AC XY:

64526

AN XY:

73704

show subpopulations

African (AFR)

AF:

0.768

AC:

31483

AN:

41014

American (AMR)

AF:

0.907

AC:

13813

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.901

AC:

3126

AN:

3470

East Asian (EAS)

AF:

0.881

AC:

4432

AN:

5032

South Asian (SAS)

AF:

0.753

AC:

3495

AN:

4640

European-Finnish (FIN)

AF:

0.975

AC:

10220

AN:

10486

Middle Eastern (MID)

AF:

0.858

AC:

247

AN:

288

European-Non Finnish (NFE)

AF:

0.921

AC:

62478

AN:

67856

Other (OTH)

AF:

0.873

AC:

1834

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

803

1606

2410

3213

4016

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

888

1776

2664

3552

4440

<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:

0.901

Hom.:

78701

Bravo

AF:

0.865

Asia WGS

AF:

0.820

AC:

2853

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

8.0

(source)

DANN

Benign

0.57

PhyloP100

0.72

PromoterAI

0.025

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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