rs148637760

Variant names:

• chr14-60483791-T-C
• rs148637760
• NM_174978.3:c.133A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_174978.3(C14orf39):​c.133A>G​(p.Lys45Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00454 in 1,531,402 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (34 hom.)
• Consequence: C14orf39 NM_174978.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.72
• Publications: 10 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004083425).
• BP6: Variant 14-60483791-T-C is Benign according to our data. Variant chr14-60483791-T-C is described in ClinVar as Benign. ClinVar VariationId is 1879279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174978.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C14orf39	NM_174978.3	MANE Select	c.133A>G	p.Lys45Glu	missense	Exon 4 of 18	NP_777638.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C14orf39	ENST00000321731.8	TSL:1 MANE Select	c.133A>G	p.Lys45Glu	missense	Exon 4 of 18	ENSP00000324920.3	Q8N1H7
	C14orf39	ENST00000557138.5	TSL:1	n.106+1090A>G		intron	N/A	ENSP00000450476.1	G3V257
	C14orf39	ENST00000917634.1		c.133A>G	p.Lys45Glu	missense	Exon 4 of 18	ENSP00000587693.1

Frequencies

GnomAD3 genomes AF: 0.00309 AC: 470 AN: 152244 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000868

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0103

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00488

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00401 AC: 945 AN: 235486 AF XY: 0.00447

Gnomad AFR exome AF: 0.000468

Gnomad AMR exome AF: 0.00236

Gnomad ASJ exome AF: 0.000207

Gnomad EAS exome AF: 0.000115

Gnomad FIN exome AF: 0.000799

Gnomad NFE exome AF: 0.00448

Gnomad OTH exome AF: 0.00494

GnomAD4 exome AF: 0.00469 AC: 6474 AN: 1379040 Hom.: 34 Cov.: 24 AF XY: 0.00490 AC XY: 3376 AN XY: 689482

African (AFR) AF: 0.000574 AC: 18 AN: 31338

American (AMR) AF: 0.00223 AC: 94 AN: 42168

Ashkenazi Jewish (ASJ) AF: 0.000276 AC: 7 AN: 25396

East Asian (EAS) AF: 0.0000259 AC: 1 AN: 38616

South Asian (SAS) AF: 0.0111 AC: 910 AN: 81950

European-Finnish (FIN) AF: 0.000887 AC: 47 AN: 52976

Middle Eastern (MID) AF: 0.00938 AC: 52 AN: 5542

European-Non Finnish (NFE) AF: 0.00478 AC: 4987 AN: 1043380

Other (OTH) AF: 0.00621 AC: 358 AN: 57674

GnomAD4 genome AF: 0.00309 AC: 471 AN: 152362 Hom.: 2 Cov.: 33 AF XY: 0.00293 AC XY: 218 AN XY: 74508

African (AFR) AF: 0.000866 AC: 36 AN: 41582

American (AMR) AF: 0.00131 AC: 20 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.0106 AC: 51 AN: 4828

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00488 AC: 332 AN: 68034

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00423 Hom.: 6

Bravo AF: 0.00286

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.00559 AC: 48

ExAC AF: 0.00406 AC: 493

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.78	T
PhyloP100		3.7
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.18
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.015	D
Vest4		0.66
MVP		0.15
MPC		0.096
ClinPred		0.025	T
GERP RS		5.7
gMVP		0.33
Mutation Taster		=95/5	polymorphism

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: rs148637760; hg19: chr14-60950509;