rs3759688

Variant names:

• chr14-60508861-A-C
• rs3759688
• ENST00000556799.1:c.-144+6534T>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000556799.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C14orf39	ENST00000556799.1	TSL:4	c.-144+6534T>G		intron	N/A	ENSP00000451441.1	G3V3U9

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

African (AFR) AF: 0.763 AC: 29 AN: 38

American (AMR) AF: 0.917 AC: 376 AN: 410

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 120 AN: 136

East Asian (EAS) AF: 0.850 AC: 51 AN: 60

South Asian (SAS) AF: 0.754 AC: 401 AN: 532

European-Finnish (FIN) AF: 0.947 AC: 305 AN: 322

Middle Eastern (MID) AF: 0.917 AC: 33 AN: 36

European-Non Finnish (NFE) AF: 0.927 AC: 6460 AN: 6966

Other (OTH) AF: 0.928 AC: 531 AN: 572

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

African (AFR) AF: 0.768 AC: 31483 AN: 41014

American (AMR) AF: 0.907 AC: 13813 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3126 AN: 3470

East Asian (EAS) AF: 0.881 AC: 4432 AN: 5032

South Asian (SAS) AF: 0.753 AC: 3495 AN: 4640

European-Finnish (FIN) AF: 0.975 AC: 10220 AN: 10486

Middle Eastern (MID) AF: 0.858 AC: 247 AN: 288

European-Non Finnish (NFE) AF: 0.921 AC: 62478 AN: 67856

Other (OTH) AF: 0.873 AC: 1834 AN: 2100

Alfa AF: 0.901 Hom.: 78701

Bravo AF: 0.865

Asia WGS AF: 0.820 AC: 2853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.0
DANN	Benign	0.57
PhyloP100		0.72
PromoterAI		0.025	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3759688; hg19: chr14-60975579;