14-60437039-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_174978.3(C14orf39):​c.1570C>A​(p.Leu524Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.067035556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C14orf39	NM_174978.3	c.1570C>A	p.Leu524Ile	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>A	p.Leu524Ile	missense_variant	Exon 18 of 18	1	NM_174978.3	ENSP00000324920.3
C14orf39	ENST00000557138.5	n.*884C>A		non_coding_transcript_exon_variant	Exon 13 of 13	1		ENSP00000450476.1
C14orf39	ENST00000557138.5	n.*884C>A		3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000450476.1
C14orf39	ENST00000498565.5	n.107-3626C>A		intron_variant	Intron 2 of 4	3		ENSP00000451937.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1446684 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 719496

African (AFR) AF: 0.00 AC: 0 AN: 32456

American (AMR) AF: 0.00 AC: 0 AN: 41634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25452

East Asian (EAS) AF: 0.00 AC: 0 AN: 39454

South Asian (SAS) AF: 0.00 AC: 0 AN: 82882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5492

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106446

Other (OTH) AF: 0.00 AC: 0 AN: 59660

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.54
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.8
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.076
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.020	D
Vest4		0.29
MutPred		0.20		Gain of methylation at K526 (P = 0.0537);
MVP		0.27
MPC		0.017
ClinPred		0.37	T
GERP RS		4.0
gMVP		0.017
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;