rs1254319

Variant names:

• chr14-60437039-G-A
• rs1254319
• NM_174978.3:c.1570C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-60437039-G-A
• chr14-60437039-G-T

Variant summary

Our verdict is Benign. The variant received -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. 12/18 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
• Publications: 59 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 (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 rank	MANE	Protein	UniProt
C14orf39	NM_174978.3	c.1570C>T	p.Leu524Phe	missense_variant	Exon 18 of 18	ENST00000321731.8	NP_777638.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C14orf39	ENST00000321731.8	c.1570C>T	p.Leu524Phe	missense_variant	Exon 18 of 18	1	NM_174978.3	ENSP00000324920.3
C14orf39	ENST00000557138.5	n.*884C>T		non_coding_transcript_exon_variant	Exon 13 of 13	1		ENSP00000450476.1
C14orf39	ENST00000557138.5	n.*884C>T		3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000450476.1
C14orf39	ENST00000498565.5	n.107-3626C>T		intron_variant	Intron 2 of 4	3		ENSP00000451937.1

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

GnomAD2 exomes AF: 0.346 AC: 82295 AN: 237618 AF XY: 0.349

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 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

African (AFR) AF: 0.503 AC: 16297 AN: 32384

American (AMR) AF: 0.242 AC: 10059 AN: 41578

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 8505 AN: 25408

East Asian (EAS) AF: 0.657 AC: 25912 AN: 39438

South Asian (SAS) AF: 0.457 AC: 37808 AN: 82770

European-Finnish (FIN) AF: 0.197 AC: 10457 AN: 53202

Middle Eastern (MID) AF: 0.437 AC: 2392 AN: 5478

European-Non Finnish (NFE) AF: 0.292 AC: 322708 AN: 1103570

Other (OTH) AF: 0.359 AC: 21344 AN: 59528

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

African (AFR) AF: 0.496 AC: 20561 AN: 41432

American (AMR) AF: 0.284 AC: 4333 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1116 AN: 3466

East Asian (EAS) AF: 0.683 AC: 3525 AN: 5160

South Asian (SAS) AF: 0.474 AC: 2277 AN: 4806

European-Finnish (FIN) AF: 0.191 AC: 2023 AN: 10564

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19958 AN: 67818

Other (OTH) AF: 0.392 AC: 828 AN: 2110

Alfa AF: 0.328 Hom.: 37059

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
PhyloP100		3.8
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1254319; hg19: chr14-60903757; COSMIC: COSV58779559;