rs1254319

chr14-60437039-G-Achr14-60437039-G-T

Variant summary

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

The NM_174978.3(C14orf39):c.1570C>T(p.Leu524Phe) variant causes a missense change. The variant allele was found at a frequency of 0.32 in 1,595,158 control chromosomes in the GnomAD database, including 88,688 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (11056 hom., cov: 32)
  • Exomes 𝑓: 0.32 (77632 hom.)
• Consequence: C14orf39 NM_174978.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.77

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 (MetaRNN=2.3323914E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C14orf39	NM_174978.3	c.1570C>T	p.Leu524Phe	missense_variant	18/18	ENST00000321731.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C14orf39	ENST00000321731.8	c.1570C>T	p.Leu524Phe	missense_variant	18/18	1	NM_174978.3	P1
C14orf39	ENST00000557138.5	c.*884C>T		3_prime_UTR_variant, NMD_transcript_variant	13/13	1
C14orf39	ENST00000498565.5	c.109-3626C>T		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54900 AN: 151686 Hom.: 11029 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.387

GnomAD3 exomes AF: 0.346 AC: 82295 AN: 237618 Hom.: 16600 AF XY: 0.349 AC XY: 44874 AN XY: 128510

Gnomad AFR exome AF: 0.501

Gnomad AMR exome AF: 0.240

Gnomad ASJ exome AF: 0.326

Gnomad EAS exome AF: 0.690

Gnomad SAS exome AF: 0.459

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.302

Gnomad OTH exome AF: 0.334

GnomAD4 exome AF: 0.316 AC: 455482 AN: 1443356 Hom.: 77632 Cov.: 31 AF XY: 0.319 AC XY: 229066 AN XY: 717982

Gnomad4 AFR exome AF: 0.503

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.335

Gnomad4 EAS exome AF: 0.657

Gnomad4 SAS exome AF: 0.457

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.359

GnomAD4 genome AF: 0.362 AC: 54964 AN: 151802 Hom.: 11056 Cov.: 32 AF XY: 0.361 AC XY: 26766 AN XY: 74196

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.392

Alfa AF: 0.325 Hom.: 20037

Bravo AF: 0.373

TwinsUK AF: 0.310 AC: 1150

ALSPAC AF: 0.297 AC: 1143

ESP6500AA AF: 0.495 AC: 2181

ESP6500EA AF: 0.295 AC: 2535

ExAC AF: 0.356 AC: 43172

Asia WGS AF: 0.570 AC: 1971 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.037
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	16
Dann	Benign	0.093
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.0000023	T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	0.96	P
PROVEAN	Benign	3.4	N
REVEL	Benign	0.069
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.091
MPC		0.017
ClinPred		0.0024	T
GERP RS		4.0
gMVP		0.011

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1254319; hg19: chr14-60903757; COSMIC: COSV58779559;