rs770570125

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080744.2(SSC4D):ā€‹c.79G>Cā€‹(p.Ala27Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 31)
Exomes š‘“: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SSC4D
NM_080744.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.07
Variant links:
Genes affected
SSC4D (HGNC:14461): (scavenger receptor cysteine rich family member with 4 domains) The scavenger receptor cysteine-rich (SRCR) superfamily is an ancient and highly conserved group of cell surface and/or secreted proteins, some of which are involved in the development of the immune system and the regulation of both innate and adaptive immune responses. Group B SRCR domains usually contain 8 regularly spaced cysteines that give rise to a well-defined intradomain disulfide-bond pattern.[supplied by OMIM, Apr 2004]
ZP3 (HGNC:13189): (zona pellucida glycoprotein 3) The zona pellucida is an extracellular matrix that surrounds the oocyte and early embryo. It is composed primarily of three or four glycoproteins with various functions during fertilization and preimplantation development. The protein encoded by this gene is a structural component of the zona pellucida and functions in primary binding and induction of the sperm acrosome reaction. The nascent protein contains a N-terminal signal peptide sequence, a conserved ZP domain, a C-terminal consensus furin cleavage site, and a transmembrane domain. It is hypothesized that furin cleavage results in release of the mature protein from the plasma membrane for subsequent incorporation into the zona pellucida matrix. However, the requirement for furin cleavage in this process remains controversial based on mouse studies. A variation in the last exon of this gene has previously served as the basis for an additional ZP3 locus; however, sequence and literature review reveals that there is only one full-length ZP3 locus in the human genome. Another locus encoding a bipartite transcript designated POMZP3 contains a duplication of the last four exons of ZP3, including the above described variation, and maps closely to this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06431931).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSC4DNM_080744.2 linkc.79G>C p.Ala27Pro missense_variant Exon 2 of 11 ENST00000275560.4 NP_542782.1 Q8WTU2-1
SSC4DXM_024446664.2 linkc.79G>C p.Ala27Pro missense_variant Exon 2 of 12 XP_024302432.1
ZP3NM_007155.6 linkc.-67+6564C>G intron_variant Intron 1 of 8 NP_009086.4 P21754-3
SSC4DXM_017011750.2 linkc.-33+5053G>C intron_variant Intron 1 of 7 XP_016867239.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SSC4DENST00000275560.4 linkc.79G>C p.Ala27Pro missense_variant Exon 2 of 11 1 NM_080744.2 ENSP00000275560.3 Q8WTU2-1
ZP3ENST00000336517.8 linkc.-67+6564C>G intron_variant Intron 1 of 8 1 ENSP00000337310.4 P21754-3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250080
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135184
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000886
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.84e-7
AC:
1
AN:
1461072
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726826
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.078
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
0.17
DANN
Benign
0.95
DEOGEN2
Benign
0.062
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.54
D
LIST_S2
Benign
0.33
T
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.064
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.6
L
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.72
N
REVEL
Benign
0.025
Sift
Benign
0.048
D
Sift4G
Benign
0.065
T
Polyphen
0.0
B
Vest4
0.14
MutPred
0.37
Gain of disorder (P = 0.0296);
MVP
0.081
MPC
0.051
ClinPred
0.061
T
GERP RS
-4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
Varity_R
0.071
gMVP
0.23

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: rs770570125; hg19: chr7-76033678; API