NM_174978.3:c.1503+5132A>G

Variant names:

• chr14-60449869-T-C
• rs1254332
• NM_174978.3:c.1503+5132A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B.

Score: -12 - Benign

-12

BP4_StrongBA1

The NM_174978.3(C14orf39):​c.1503+5132A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,236 control chromosomes in the GnomAD database, including 4,052 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 0.18 (4052 hom., cov: 32)
• Consequence: C14orf39 NM_174978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C14orf39	NM_174978.3	c.1503+5132A>G		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+5132A>G		intron_variant	Intron 16 of 17	1	NM_174978.3	ENSP00000324920.3
C14orf39	ENST00000557138.5	n.*817+5132A>G		intron_variant	Intron 11 of 12	1		ENSP00000450476.1
C14orf39	ENST00000498565.5	n.48+5132A>G		intron_variant	Intron 1 of 4	3		ENSP00000451937.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27068 AN: 152118 Hom.: 4039 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0810

Gnomad OTH AF: 0.169

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.178 AC: 27120 AN: 152236 Hom.: 4052 Cov.: 32 AF XY: 0.175 AC XY: 13039 AN XY: 74458

African (AFR) AF: 0.403 AC: 16716 AN: 41500

American (AMR) AF: 0.117 AC: 1791 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3470

East Asian (EAS) AF: 0.144 AC: 748 AN: 5182

South Asian (SAS) AF: 0.263 AC: 1270 AN: 4824

European-Finnish (FIN) AF: 0.0258 AC: 274 AN: 10628

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.0810 AC: 5509 AN: 68024

Other (OTH) AF: 0.169 AC: 356 AN: 2108

Alfa AF: 0.113 Hom.: 346

Bravo AF: 0.192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	9.9
DANN	Benign	0.72
PhyloP100		-0.052
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: rs1254332; hg19: chr14-60916587;