Variant 14-60456996-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_174978.3(C14orf39):c.1279T>C(p.Phe427Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00355 in 1,611,372 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0037 ( 17 hom. )

Consequence

C14orf39
NM_174978.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.15

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008772612).

BP6

Variant 14-60456996-A-G is Benign according to our data. Variant chr14-60456996-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3055519.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C14orf39	NM_174978.3 linkuse as main transcript	c.1279T>C	p.Phe427Leu	missense_variant	15/18	ENST00000321731.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C14orf39	ENST00000321731.8 linkuse as main transcript	c.1279T>C	p.Phe427Leu	missense_variant	15/18	1	NM_174978.3	P1
C14orf39	ENST00000557138.5 linkuse as main transcript	c.*593T>C		3_prime_UTR_variant, NMD_transcript_variant	10/13	1

Frequencies

GnomAD3 genomes

AF:

0.00228

AC:

347

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00366

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00228

AC:

568

AN:

249488

Hom.:

AF XY:

0.00232

AC XY:

313

AN XY:

134990

show subpopulations

Gnomad AFR exome

AF:

0.00107

Gnomad AMR exome

AF:

0.00126

Gnomad ASJ exome

AF:

0.000499

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000657

Gnomad FIN exome

AF:

0.00227

Gnomad NFE exome

AF:

0.00388

Gnomad OTH exome

AF:

0.00215

GnomAD4 exome

AF:

0.00368

AC:

5371

AN:

1459204

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

2553

AN XY:

725888

show subpopulations

Gnomad4 AFR exome

AF:

0.000841

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.000384

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00285

Gnomad4 NFE exome

AF:

0.00447

Gnomad4 OTH exome

AF:

0.00259

GnomAD4 genome

AF:

0.00228

AC:

347

AN:

152168

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

157

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.000915

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.00366

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00329

Hom.:

Bravo

AF:

0.00216

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00243

AC:

295

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

C14orf39-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 11, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

0.13

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.52

M_CAP

Benign

0.012

MetaRNN

Benign

0.0088

MetaSVM

Benign

-0.90

MutationTaster

Benign

0.61

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.11

Sift

Uncertain

0.026

Sift4G

Pathogenic

0.0

Vest4

0.42

MutPred

0.33

Loss of methylation at K432 (P = 0.073);

MVP

0.072

MPC

0.071

ClinPred

0.042

GERP RS

4.2

gMVP

0.062

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