14-20770507-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022360.5(EDDM3B):​c.357C>G​(p.Ser119Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

EDDM3B
NM_022360.5 missense

Scores

2
5
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.559
Variant links:
Genes affected
EDDM3B (HGNC:19223): (epididymal protein 3B) Testicular sperm are morphologically differentiated but are not progressively motile nor able to fertilize an egg. Post-testicular maturation requires exposure of spermatozoa to the microenvironment of the epididymal lumen. Spermatozoa undergo extensive changes in the epididymis, including enzymatic modifications, loss of pre-existing components and addition of new glycoproteins from epididymal secretions. These modifying proteins and enzymes are synthesized by epithelial cells lining the epididymal duct and secreted apically into the lumen, where they come into contact with, and may be absorbed onto, the sperm membranes. The proteins encoded by the genes in this cluster are synthesized and secreted by epididymal epithelial cells. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31203982).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EDDM3BNM_022360.5 linkc.357C>G p.Ser119Arg missense_variant Exon 2 of 2 ENST00000326783.4 NP_071755.1 P56851W0UV31
LOC107984671XR_001750622.2 linkn.627-7664G>C intron_variant Intron 1 of 2
LOC107984671XR_001750623.2 linkn.627-7664G>C intron_variant Intron 1 of 3
LOC107984671XR_001750624.2 linkn.627-7664G>C intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EDDM3BENST00000326783.4 linkc.357C>G p.Ser119Arg missense_variant Exon 2 of 2 1 NM_022360.5 ENSP00000314810.3 P56851

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251040
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135664
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000993
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461868
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000434
Hom.:
0
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.83
BayesDel_addAF
Uncertain
0.019
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T
Eigen
Benign
0.015
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.45
T
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-0.62
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.44
T
PROVEAN
Pathogenic
-4.6
D
REVEL
Benign
0.29
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.0070
D
Polyphen
0.99
D
Vest4
0.40
MutPred
0.26
Gain of sheet (P = 0.039);
MVP
0.89
MPC
0.26
ClinPred
0.99
D
GERP RS
1.0
Varity_R
0.49
gMVP
0.41

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs778679067; hg19: chr14-21238666; API