XM_017021250.3:c.-3995C>G

Variant names:

• chr14-60503286-G-C
• rs7160405
• XM_017021250.3:c.-3995C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017021250.3(C14orf39):​c.-3995C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 152,016 control chromosomes in the GnomAD database, including 53,550 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 0.83 (53550 hom., cov: 30)
• Consequence: C14orf39 XM_017021250.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C14orf39	XM_017021250.3	c.-3995C>G		5_prime_UTR_variant	Exon 1 of 14		XP_016876739.1
C14orf39	XM_047431324.1	c.-143-3856C>G		intron_variant	Intron 1 of 18		XP_047287280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C14orf39	ENST00000556799.1	c.-143-3856C>G		intron_variant	Intron 1 of 5	4		ENSP00000451441.1

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125747 AN: 151898 Hom.: 53526 Cov.: 30

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.946

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.919

Gnomad OTH AF: 0.837

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.828 AC: 125823 AN: 152016 Hom.: 53550 Cov.: 30 AF XY: 0.830 AC XY: 61706 AN XY: 74318

African (AFR) AF: 0.616 AC: 25459 AN: 41358

American (AMR) AF: 0.888 AC: 13564 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 3123 AN: 3472

East Asian (EAS) AF: 0.855 AC: 4411 AN: 5160

South Asian (SAS) AF: 0.738 AC: 3554 AN: 4818

European-Finnish (FIN) AF: 0.975 AC: 10330 AN: 10600

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.919 AC: 62516 AN: 68008

Other (OTH) AF: 0.837 AC: 1767 AN: 2112

Alfa AF: 0.870 Hom.: 3453

Bravo AF: 0.815

Asia WGS AF: 0.788 AC: 2742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.49
PhyloP100		0.0060

Splicing

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

Other links and lift over

dbSNP: rs7160405; hg19: chr14-60970004;