14-60464648-C-T

Position:

• chr14-60464648-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_174978.3(C14orf39):​c.972+1331G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00555 in 152,178 control chromosomes in the GnomAD database, including 2 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 0.0056 (2 hom., cov: 33)
• Consequence: C14orf39 NM_174978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374

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=-1.02).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00555 (845/152178) while in subpopulation AFR AF= 0.0182 (757/41540). AF 95% confidence interval is 0.0171. There are 2 homozygotes in gnomad4. There are 381 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C14orf39	NM_174978.3	c.972+1331G>A		intron_variant		ENST00000321731.8	NP_777638.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C14orf39	ENST00000321731.8	c.972+1331G>A		intron_variant		1	NM_174978.3	ENSP00000324920	P1
C14orf39	ENST00000557138.5	c.*286+1331G>A		intron_variant, NMD_transcript_variant		1		ENSP00000450476

Frequencies

GnomAD3 genomes AF: 0.00550 AC: 836 AN: 152060 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00446

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00573

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

GnomAD4 genome AF: 0.00555 AC: 845 AN: 152178 Hom.: 2 Cov.: 33 AF XY: 0.00512 AC XY: 381 AN XY: 74400

Gnomad4 AFR AF: 0.0182

Gnomad4 AMR AF: 0.00445

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00284 Hom.: 0

Bravo AF: 0.00642

Asia WGS AF: 0.00202 AC: 7 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.66

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: rs10483724; hg19: chr14-60931366;