14-60453807-A-T

Variant names:

• chr14-60453807-A-T
• rs1254337
• NM_174978.3:c.1503+1194T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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=-0.95).
• 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 rank	MANE	Protein	UniProt
C14orf39	NM_174978.3	c.1503+1194T>A		intron_variant	Intron 16 of 17	ENST00000321731.8	NP_777638.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C14orf39	ENST00000321731.8	c.1503+1194T>A		intron_variant	Intron 16 of 17	1	NM_174978.3	ENSP00000324920.3
C14orf39	ENST00000557138.5	n.*817+1194T>A		intron_variant	Intron 11 of 12	1		ENSP00000450476.1
C14orf39	ENST00000498565.5	n.48+1194T>A		intron_variant	Intron 1 of 4	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

African (AFR) AF: 0.496 AC: 20547 AN: 41428

American (AMR) AF: 0.293 AC: 4466 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1169 AN: 3460

East Asian (EAS) AF: 0.688 AC: 3552 AN: 5164

South Asian (SAS) AF: 0.474 AC: 2288 AN: 4822

European-Finnish (FIN) AF: 0.194 AC: 2042 AN: 10552

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.306 AC: 20703 AN: 67738

Other (OTH) AF: 0.401 AC: 844 AN: 2104

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
PhyloP100		0.093
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1254337; hg19: chr14-60920525;