rs3759688

Positions:

• chr14-60508861-A-C
• chr14-60508861-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000556799.1(C14orf39):​c.-144+6534T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 160,092 control chromosomes in the GnomAD database, including 61,871 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.87 (58060 hom., cov: 26)
  • Exomes 𝑓: 0.92 (3811 hom.)
• Consequence: C14orf39 ENST00000556799.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C14orf39	XM_047431324.1	c.-144+6534T>G		intron_variant			XP_047287280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C14orf39	ENST00000556799.1	c.-144+6534T>G		intron_variant		4		ENSP00000451441.1

Frequencies

GnomAD3 genomes AF: 0.874 AC: 131864 AN: 150890 Hom.: 58002 Cov.: 26

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.946

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.872

GnomAD4 exome AF: 0.916 AC: 8306 AN: 9072 Hom.: 3811 AF XY: 0.907 AC XY: 3866 AN XY: 4262

Gnomad4 AFR exome AF: 0.763

Gnomad4 AMR exome AF: 0.917

Gnomad4 ASJ exome AF: 0.882

Gnomad4 EAS exome AF: 0.850

Gnomad4 SAS exome AF: 0.754

Gnomad4 FIN exome AF: 0.947

Gnomad4 NFE exome AF: 0.927

Gnomad4 OTH exome AF: 0.928

GnomAD4 genome AF: 0.874 AC: 131987 AN: 151020 Hom.: 58060 Cov.: 26 AF XY: 0.875 AC XY: 64526 AN XY: 73704

Gnomad4 AFR AF: 0.768

Gnomad4 AMR AF: 0.907

Gnomad4 ASJ AF: 0.901

Gnomad4 EAS AF: 0.881

Gnomad4 SAS AF: 0.753

Gnomad4 FIN AF: 0.975

Gnomad4 NFE AF: 0.921

Gnomad4 OTH AF: 0.873

Alfa AF: 0.907 Hom.: 60391

Bravo AF: 0.865

Asia WGS AF: 0.820 AC: 2853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.0
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3759688; hg19: chr14-60975579;