Genetic Variant NM_174978.3:c.204_205delTA (chr14-60483718-CTA-C) – ACMG Classification: Pathogenic (11 pts)

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_174978.3(C14orf39):c.204_205delTA(p.His68GlnfsTer2) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000138 in 1,445,038 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

C14orf39
NM_174978.3 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:4

Conservation

PhyloP100: 3.72

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:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 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 14-60483718-CTA-C is Pathogenic according to our data. Variant chr14-60483718-CTA-C is described in ClinVar as [Pathogenic]. Clinvar id is 992822.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-60483718-CTA-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C14orf39	NM_174978.3 link	c.204_205delTA	p.His68GlnfsTer2	frameshift_variant	Exon 4 of 18	ENST00000321731.8	NP_777638.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C14orf39	ENST00000321731.8 link	c.204_205delTA	p.His68GlnfsTer2	frameshift_variant	Exon 4 of 18	1	NM_174978.3	ENSP00000324920.3	Q8N1H7
C14orf39	ENST00000557138.5 link	n.106+1161_106+1162delTA		intron_variant	Intron 3 of 12	1		ENSP00000450476.1	G3V257
C14orf39	ENST00000555476.5 link	c.117_118delTA	p.His39GlnfsTer2	frameshift_variant	Exon 3 of 5	5		ENSP00000451665.1	G3V493
C14orf39	ENST00000556799.1 link	c.204_205delTA	p.His68GlnfsTer2	frameshift_variant	Exon 5 of 6	4		ENSP00000451441.1	G3V3U9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000414

AC:

AN:

241674

Hom.:

AF XY:

0.00000765

AC XY:

AN XY:

130734

show subpopulations

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:

0.00000903

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1445038

Hom.:

AF XY:

0.00000278

AC XY:

AN XY:

719214

show subpopulations

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:

0.00000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:4

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Spermatogenic failure 52

Pathogenic:1

Feb 23, 2021

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Premature ovarian failure 18

Pathogenic:1

Feb 23, 2021

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Non-obstructive azoospermia

Pathogenic:1

Nov 14, 2018

Molecular and Cell Genetics Laboratory, University of Science and Technology of China

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Azoospermia

Pathogenic:1

Dec 20, 2021

Genetics of Infertility and Preimplantation Genetic Diagnosis, Centre Hospitalier Universitaire Grenoble Alpes

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: case-control

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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