chr14-60483781-ATAGT-A

Variant names:

• chr14-60483781-ATAGT-A
• rs1182145636
• NM_174978.3:c.139_142delACTA

Variant summary

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

The NM_174978.3(C14orf39):​c.139_142delACTA​(p.Thr47PhefsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,395,764 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: C14orf39 NM_174978.3 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.977

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 14-60483781-ATAGT-A is Pathogenic according to our data. Variant chr14-60483781-ATAGT-A is described in ClinVar as [Pathogenic]. Clinvar id is 3390936.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.139_142delACTA	p.Thr47PhefsTer8	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.139_142delACTA	p.Thr47PhefsTer8	frameshift_variant	Exon 4 of 18	1	NM_174978.3	ENSP00000324920.3
C14orf39	ENST00000557138.5	n.106+1096_106+1099delACTA		intron_variant	Intron 3 of 12	1		ENSP00000450476.1
C14orf39	ENST00000555476.5	c.52_55delACTA	p.Thr18PhefsTer8	frameshift_variant	Exon 3 of 5	5		ENSP00000451665.1
C14orf39	ENST00000556799.1	c.139_142delACTA	p.Thr47PhefsTer8	frameshift_variant	Exon 5 of 6	4		ENSP00000451441.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000417 AC: 1 AN: 239758 Hom.: 0 AF XY: 0.00000771 AC XY: 1 AN XY: 129706

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000314

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1395764 Hom.: 0 AF XY: 0.00000143 AC XY: 1 AN XY: 697408

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.46e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spermatogenic failure 52 Pathogenic:1

Dec 17, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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: rs1182145636; hg19: chr14-60950499;