Variant 14-60483791-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_174978.3(C14orf39):c.133A>G(p.Lys45Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00454 in 1,531,402 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0047 ( 34 hom. )

Consequence

C14orf39
NM_174978.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.72

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004083425).

BP6

Variant 14-60483791-T-C is Benign according to our data. Variant chr14-60483791-T-C is described in ClinVar as [Benign]. Clinvar id is 1879279.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C14orf39	NM_174978.3 linkuse as main transcript	c.133A>G	p.Lys45Glu	missense_variant	4/18	ENST00000321731.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
C14orf39	ENST00000321731.8 linkuse as main transcript	c.133A>G	p.Lys45Glu	missense_variant	4/18	1	NM_174978.3	P1
C14orf39	ENST00000557138.5 linkuse as main transcript	c.106+1090A>G		intron_variant, NMD_transcript_variant		1
C14orf39	ENST00000555476.5 linkuse as main transcript	c.46A>G	p.Lys16Glu	missense_variant	3/5	5
C14orf39	ENST00000556799.1 linkuse as main transcript	c.133A>G	p.Lys45Glu	missense_variant	5/6	4

Frequencies

GnomAD3 genomes

AF:

0.00309

AC:

470

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0103

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00488

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00401

AC:

945

AN:

235486

Hom.:

AF XY:

0.00447

AC XY:

569

AN XY:

127316

show subpopulations

Gnomad AFR exome

AF:

0.000468

Gnomad AMR exome

AF:

0.00236

Gnomad ASJ exome

AF:

0.000207

Gnomad EAS exome

AF:

0.000115

Gnomad SAS exome

AF:

0.0121

Gnomad FIN exome

AF:

0.000799

Gnomad NFE exome

AF:

0.00448

Gnomad OTH exome

AF:

0.00494

GnomAD4 exome

AF:

0.00469

AC:

6474

AN:

1379040

Hom.:

Cov.:

AF XY:

0.00490

AC XY:

3376

AN XY:

689482

show subpopulations

Gnomad4 AFR exome

AF:

0.000574

Gnomad4 AMR exome

AF:

0.00223

Gnomad4 ASJ exome

AF:

0.000276

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.0111

Gnomad4 FIN exome

AF:

0.000887

Gnomad4 NFE exome

AF:

0.00478

Gnomad4 OTH exome

AF:

0.00621

GnomAD4 genome

AF:

0.00309

AC:

471

AN:

152362

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

218

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00488

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00440

Hom.:

Bravo

AF:

0.00286

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00559

AC:

ExAC

AF:

0.00406

AC:

493

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

C14orf39: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.65

T;T;T

MetaRNN

Benign

0.0041

T;T;T

MetaSVM

Benign

-0.78

MutationTaster

Benign

0.96

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0050

D;D;D

Sift4G

Uncertain

0.015

D;.;.

Vest4

0.66

MVP

0.15

MPC

0.096

ClinPred

0.025

GERP RS

5.7

gMVP

0.33

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

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