rs145164745

Variant names:

• chr14-60436905-A-C
• rs145164745
• NM_174978.3:c.1704T>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.1704T>G​(p.Ser568Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,612,670 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00042 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000089 (3 hom.)
• Consequence: C14orf39 NM_174978.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.39
• Publications: 0 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=-0.53).
• BP6: Variant 14-60436905-A-C is Benign according to our data. Variant chr14-60436905-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2644267.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.39 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 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.1704T>G	p.Ser568Ser	synonymous	Exon 18 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.1704T>G	p.Ser568Ser	synonymous	Exon 18 of 18	ENSP00000324920.3	Q8N1H7
	C14orf39	ENST00000557138.5	TSL:1	n.*1018T>G		non_coding_transcript_exon	Exon 13 of 13	ENSP00000450476.1	G3V257
	C14orf39	ENST00000557138.5	TSL:1	n.*1018T>G		3_prime_UTR	Exon 13 of 13	ENSP00000450476.1	G3V257

Frequencies

GnomAD3 genomes AF: 0.000421 AC: 64 AN: 152072 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000140 AC: 35 AN: 250752 AF XY: 0.000133

Gnomad AFR exome AF: 0.000930

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000816

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.0000890 AC: 130 AN: 1460598 Hom.: 3 Cov.: 30 AF XY: 0.0000729 AC XY: 53 AN XY: 726636

African (AFR) AF: 0.000538 AC: 18 AN: 33438

American (AMR) AF: 0.0000224 AC: 1 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.000430 AC: 17 AN: 39528

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111216

Other (OTH) AF: 0.00143 AC: 86 AN: 60338

GnomAD4 genome AF: 0.000421 AC: 64 AN: 152072 Hom.: 1 Cov.: 32 AF XY: 0.000377 AC XY: 28 AN XY: 74298

African (AFR) AF: 0.00121 AC: 50 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15256

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

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67954

Other (OTH) AF: 0.000957 AC: 2 AN: 2090

Alfa AF: 0.000255 Hom.: 0

Bravo AF: 0.000404

Asia WGS AF: 0.00260 AC: 9 AN: 3472

ClinVar

ClinVar submissions as Germline

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	-0.53
CADD	Benign	5.8
DANN	Benign	0.73
PhyloP100		2.4
Mutation Taster		=100/0	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: rs145164745; hg19: chr14-60903623;