14-60483713-CCTCA-C

Variant names:

• chr14-60483713-CCTCA-C
• rs748322684
• NM_174978.3:c.207_210delTGAG

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_174978.3(C14orf39):​c.207_210delTGAG​(p.Ser69ArgfsTer53) variant causes a frameshift change. The variant allele was found at a frequency of 0.000018 in 1,444,296 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: C14orf39 NM_174978.3 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.72

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]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 14-60483713-CCTCA-C is Pathogenic according to our data. Variant chr14-60483713-CCTCA-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3899291.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C14orf39	NM_174978.3	c.207_210delTGAG	p.Ser69ArgfsTer53	frameshift_variant	Exon 4 of 18	ENST00000321731.8	NP_777638.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C14orf39	ENST00000321731.8	c.207_210delTGAG	p.Ser69ArgfsTer53	frameshift_variant	Exon 4 of 18	1	NM_174978.3	ENSP00000324920.3
C14orf39	ENST00000557138.5	n.106+1164_106+1167delTGAG		intron_variant	Intron 3 of 12	1		ENSP00000450476.1
C14orf39	ENST00000555476.5	c.120_123delTGAG	p.Ser40ArgfsTer53	frameshift_variant	Exon 3 of 5	5		ENSP00000451665.1
C14orf39	ENST00000556799.1	c.207_210delTGAG	p.Ser69ArgfsTer19	frameshift_variant	Exon 5 of 6	4		ENSP00000451441.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000208 AC: 5 AN: 240296 Hom.: 0 AF XY: 0.0000231 AC XY: 3 AN XY: 129994

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000453

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000180 AC: 26 AN: 1444296 Hom.: 0 AF XY: 0.0000209 AC XY: 15 AN XY: 718786

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000235

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000218

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spermatogenic failure 52;C5543095:Premature ovarian failure 18 Pathogenic:1

Jan 06, 2025

First Genomix Gene Laboratory, Genetic Diagnostics Department

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

As part of Carrier Screening testing performed at First Genomix, this variant was identified in a heterozygous state in a patient who is not affected with this condition. -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs748322684; hg19: chr14-60950431;