Genetic Variant NM_174978.3:c.1386A>C (chr14-60455118-T-G) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_174978.3(C14orf39):c.1386A>C(p.Glu462Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00477 in 1,564,472 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 19 hom. )

Consequence

C14orf39
NM_174978.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.64

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=0.004501492).

BP6

Variant 14-60455118-T-G is Benign according to our data. Variant chr14-60455118-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2644268.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C14orf39	NM_174978.3 link	c.1386A>C	p.Glu462Asp	missense_variant	Exon 16 of 18	ENST00000321731.8	NP_777638.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C14orf39	ENST00000321731.8 link	c.1386A>C	p.Glu462Asp	missense_variant	Exon 16 of 18	1	NM_174978.3	ENSP00000324920.3	Q8N1H7
C14orf39	ENST00000557138.5 link	n.*700A>C		non_coding_transcript_exon_variant	Exon 11 of 13	1		ENSP00000450476.1	G3V257
C14orf39	ENST00000557138.5 link	n.*700A>C		3_prime_UTR_variant	Exon 11 of 13	1		ENSP00000450476.1	G3V257
C14orf39	ENST00000498565.5 link	n.-70A>C		upstream_gene_variant		3		ENSP00000451937.1	H0YJQ0

Frequencies

GnomAD3 genomes

AF:

0.00295

AC:

449

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00158

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00534

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00279

AC:

576

AN:

206180

Hom.:

AF XY:

0.00289

AC XY:

326

AN XY:

112796

show subpopulations

Gnomad AFR exome

AF:

0.000942

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.000126

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000661

Gnomad FIN exome

AF:

0.00154

Gnomad NFE exome

AF:

0.00460

Gnomad OTH exome

AF:

0.00355

GnomAD4 exome

AF:

0.00497

AC:

7014

AN:

1412344

Hom.:

Cov.:

AF XY:

0.00478

AC XY:

3360

AN XY:

703042

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00204

Gnomad4 ASJ exome

AF:

0.0000828

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000714

Gnomad4 FIN exome

AF:

0.00185

Gnomad4 NFE exome

AF:

0.00601

Gnomad4 OTH exome

AF:

0.00300

GnomAD4 genome

AF:

0.00296

AC:

450

AN:

152128

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

206

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00189

Gnomad4 NFE

AF:

0.00535

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00444

Hom.:

Bravo

AF:

0.00289

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.00489

AC:

ExAC

AF:

0.00268

AC:

325

Asia WGS

AF:

0.000869

AC:

AN:

3468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

C14orf39: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.48

M_CAP

Benign

0.0066

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.75

REVEL

Benign

0.062

Sift

Benign

0.20

Sift4G

Pathogenic

0.0

Vest4

0.23

MutPred

0.12

Loss of methylation at K467 (P = 0.1893);

MVP

0.39

MPC

0.088

ClinPred

0.024

GERP RS

2.1

gMVP

0.046

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