14-60471601-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_174978.3(C14orf39):c.462A>G(p.Ala154=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00621 in 1,610,426 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0045 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (52 hom.)
• Consequence: C14orf39 NM_174978.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.47

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 14-60471601-T-C is Benign according to our data. Variant chr14-60471601-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2644269.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.47 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C14orf39	NM_174978.3	c.462A>G	p.Ala154=	synonymous_variant	6/18	ENST00000321731.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C14orf39	ENST00000321731.8	c.462A>G	p.Ala154=	synonymous_variant	6/18	1	NM_174978.3	P1
C14orf39	ENST00000557138.5	c.107-3068A>G		intron_variant, NMD_transcript_variant		1
C14orf39	ENST00000555476.5			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.00448 AC: 681 AN: 152018 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00558

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.00696

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00521 AC: 1295 AN: 248494 Hom.: 7 AF XY: 0.00543 AC XY: 729 AN XY: 134278

Gnomad AFR exome AF: 0.00161

Gnomad AMR exome AF: 0.00308

Gnomad ASJ exome AF: 0.00601

Gnomad EAS exome AF: 0.0000546

Gnomad SAS exome AF: 0.00567

Gnomad FIN exome AF: 0.000929

Gnomad NFE exome AF: 0.00787

Gnomad OTH exome AF: 0.00462

GnomAD4 exome AF: 0.00639 AC: 9316 AN: 1458290 Hom.: 52 Cov.: 31 AF XY: 0.00651 AC XY: 4725 AN XY: 725368

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.00320

Gnomad4 ASJ exome AF: 0.00527

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00589

Gnomad4 FIN exome AF: 0.00154

Gnomad4 NFE exome AF: 0.00717

Gnomad4 OTH exome AF: 0.00671

GnomAD4 genome AF: 0.00447 AC: 680 AN: 152136 Hom.: 7 Cov.: 32 AF XY: 0.00376 AC XY: 280 AN XY: 74382

Gnomad4 AFR AF: 0.00132

Gnomad4 AMR AF: 0.00557

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00581

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00696

Gnomad4 OTH AF: 0.00664

Alfa AF: 0.00641 Hom.: 3

Bravo AF: 0.00471

Asia WGS AF: 0.00261 AC: 10 AN: 3466

EpiCase AF: 0.00837

EpiControl AF: 0.00860

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

C14orf39: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	9.8
Dann	Benign	0.74

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: rs35543839; hg19: chr14-60938319;