Genetic Variant NM_174978.3:c.1570C>A (chr14-60437039-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_174978.3(C14orf39):c.1570C>A(p.Leu524Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

C14orf39
NM_174978.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.77

Publications

59 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.067035556).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C14orf39	NM_174978.3	MANE Select	c.1570C>A	p.Leu524Ile	missense	Exon 18 of 18	NP_777638.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
C14orf39	ENST00000321731.8	TSL:1 MANE Select	c.1570C>A	p.Leu524Ile	missense	Exon 18 of 18	ENSP00000324920.3
C14orf39	ENST00000557138.5	TSL:1	n.*884C>A		non_coding_transcript_exon	Exon 13 of 13	ENSP00000450476.1
C14orf39	ENST00000557138.5	TSL:1	n.*884C>A		3_prime_UTR	Exon 13 of 13	ENSP00000450476.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1446684

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719496

African (AFR)

AF:

0.00

AC:

AN:

32456

American (AMR)

AF:

0.00

AC:

AN:

41634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25452

East Asian (EAS)

AF:

0.00

AC:

AN:

39454

South Asian (SAS)

AF:

0.00

AC:

AN:

82882

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5492

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106446

Other (OTH)

AF:

0.00

AC:

AN:

59660

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.40

M_CAP

Benign

0.0093

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.1

PhyloP100

3.8

PROVEAN

Benign

-0.030

REVEL

Benign

0.076

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.020

Vest4

0.29

MutPred

0.20

Gain of methylation at K526 (P = 0.0537)

MVP

0.27

MPC

0.017

ClinPred

0.37

GERP RS

4.0

gMVP

0.017

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over