Genetic Variant EDDM3B:p.Cys16Tyr (chr14-20770197-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022360.5(EDDM3B):c.47G>A(p.Cys16Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,262 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C16F) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 1 hom., cov: 32)

Consequence

EDDM3B
NM_022360.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.696

Publications

0 publications found

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]

EDDM3B links:

ENSG00000303727 (HGNC:):

ENSG00000303727 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1487374).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022360.5. 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
	EDDM3B	NM_022360.5	MANE Select	c.47G>A	p.Cys16Tyr	missense	Exon 2 of 2	NP_071755.1	P56851

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EDDM3B	ENST00000326783.4	TSL:1 MANE Select	c.47G>A	p.Cys16Tyr	missense	Exon 2 of 2	ENSP00000314810.3	P56851
ENSG00000303727	ENST00000796740.1		n.79-7354C>T		intron	N/A
ENSG00000303727	ENST00000796741.1		n.72-7354C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41546

American (AMR)

AF:

0.000131

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2110

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.31

DEOGEN2

Benign

0.16

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.55

M_CAP

Benign

0.0050

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

0.70

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.061

Sift

Benign

0.57

Sift4G

Benign

0.88

Polyphen

0.51

Vest4

0.28

MutPred

0.60

Gain of catalytic residue at L11 (P = 0.0876)

MVP

0.25

MPC

0.045

ClinPred

0.77

GERP RS

3.0

Varity_R

0.079

gMVP

0.22

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over