14-60471601-T-C

Variant names:

• chr14-60471601-T-C
• rs35543839
• NM_174978.3:c.462A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_174978.3(C14orf39):​c.462A>G​(p.Ala154Ala) 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
• Publications: 2 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 -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 VariationId 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 GnomAd4 at 7 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.462A>G	p.Ala154Ala	synonymous	Exon 6 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.462A>G	p.Ala154Ala	synonymous	Exon 6 of 18	ENSP00000324920.3	Q8N1H7
	C14orf39	ENST00000557138.5	TSL:1	n.107-3068A>G		intron	N/A	ENSP00000450476.1	G3V257
	C14orf39	ENST00000917634.1		c.462A>G	p.Ala154Ala	synonymous	Exon 6 of 18	ENSP00000587693.1

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

GnomAD2 exomes AF: 0.00521 AC: 1295 AN: 248494 AF XY: 0.00543

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 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

African (AFR) AF: 0.00111 AC: 37 AN: 33314

American (AMR) AF: 0.00320 AC: 142 AN: 44326

Ashkenazi Jewish (ASJ) AF: 0.00527 AC: 137 AN: 25990

East Asian (EAS) AF: 0.00 AC: 0 AN: 39526

South Asian (SAS) AF: 0.00589 AC: 504 AN: 85598

European-Finnish (FIN) AF: 0.00154 AC: 82 AN: 53326

Middle Eastern (MID) AF: 0.00958 AC: 55 AN: 5740

European-Non Finnish (NFE) AF: 0.00717 AC: 7955 AN: 1110258

Other (OTH) AF: 0.00671 AC: 404 AN: 60212

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

African (AFR) AF: 0.00132 AC: 55 AN: 41554

American (AMR) AF: 0.00557 AC: 85 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3464

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00581 AC: 28 AN: 4820

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10620

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.00696 AC: 473 AN: 67928

Other (OTH) AF: 0.00664 AC: 14 AN: 2110

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

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.49
CADD	Benign	9.8
DANN	Benign	0.74
PhyloP100		1.5
Mutation Taster		=99/1	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: rs35543839; hg19: chr14-60938319; COSMIC: COSV108152582; COSMIC: COSV108152582;