Genetic Variant C14orf39:p.Asn201Ser (chr14-60469606-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_174978.3(C14orf39):c.602A>G(p.Asn201Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000493 in 1,522,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

C14orf39
NM_174978.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.349

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0423674).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174978.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C14orf39	NM_174978.3	MANE Select	c.602A>G	p.Asn201Ser	missense	Exon 8 of 18	NP_777638.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C14orf39	ENST00000321731.8	TSL:1 MANE Select	c.602A>G	p.Asn201Ser	missense	Exon 8 of 18	ENSP00000324920.3	Q8N1H7
C14orf39	ENST00000557138.5	TSL:1	n.107-1073A>G		intron	N/A	ENSP00000450476.1	G3V257
C14orf39	ENST00000917634.1		c.602A>G	p.Asn201Ser	missense	Exon 8 of 18	ENSP00000587693.1

Frequencies

GnomAD3 genomes

AF:

0.0000859

AC:

AN:

151262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000592

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000766

AC:

AN:

222010

AF XY:

0.0000744

show subpopulations

Gnomad AFR exome

AF:

0.000209

Gnomad AMR exome

AF:

0.0000379

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000642

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000952

Gnomad OTH exome

AF:

0.000192

GnomAD4 exome

AF:

0.0000452

AC:

AN:

1371044

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

681646

show subpopulations

African (AFR)

AF:

0.0000973

AC:

AN:

30824

American (AMR)

AF:

0.0000270

AC:

AN:

36972

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24004

East Asian (EAS)

AF:

0.0000542

AC:

AN:

36912

South Asian (SAS)

AF:

0.0000566

AC:

AN:

70672

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5436

European-Non Finnish (NFE)

AF:

0.0000472

AC:

AN:

1059666

Other (OTH)

AF:

0.0000357

AC:

AN:

55988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000859

AC:

AN:

151262

Hom.:

Cov.:

AF XY:

0.0000812

AC XY:

AN XY:

73870

show subpopulations

African (AFR)

AF:

0.000218

AC:

AN:

41352

American (AMR)

AF:

0.00

AC:

AN:

15118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000592

AC:

AN:

67616

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000848

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000292

AC:

AN:

3438

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.4

(source)

DANN

Benign

0.35

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.53

M_CAP

Benign

0.0045

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.96

PhyloP100

-0.35

PROVEAN

Benign

-0.30

REVEL

Benign

0.049

Sift

Benign

0.47

Sift4G

Benign

0.60

Vest4

0.098

MVP

0.095

MPC

0.016

ClinPred

0.034

GERP RS

-2.1

gMVP

0.022

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over