14-60453807-A-T

Position:

• chr14-60453807-A-T

Variant summary

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

The NM_174978.3(C14orf39):​c.1503+1194T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,700 control chromosomes in the GnomAD database, including 11,376 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 0.37 (11376 hom., cov: 32)
• Consequence: C14orf39 NM_174978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C14orf39	NM_174978.3	c.1503+1194T>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.1503+1194T>A		intron_variant		1	NM_174978.3	ENSP00000324920.3
C14orf39	ENST00000557138.5	n.*817+1194T>A		intron_variant		1		ENSP00000450476.1
C14orf39	ENST00000498565.5	n.48+1194T>A		intron_variant		3		ENSP00000451937.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55946 AN: 151584 Hom.: 11348 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.369 AC: 56009 AN: 151700 Hom.: 11376 Cov.: 32 AF XY: 0.367 AC XY: 27234 AN XY: 74138

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.401

Alfa AF: 0.324 Hom.: 1051

Bravo AF: 0.381

Asia WGS AF: 0.577 AC: 1985 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.2
DANN	Benign	0.60

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: rs1254337; hg19: chr14-60920525;