rs770570125
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_080744.2(SSC4D):āc.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
NM_080744.2 missense
Scores
19
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.07
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 |
---|---|---|---|---|---|---|---|---|
SSC4D | NM_080744.2 | c.79G>C | p.Ala27Pro | missense_variant | Exon 2 of 11 | ENST00000275560.4 | NP_542782.1 | |
SSC4D | XM_024446664.2 | c.79G>C | p.Ala27Pro | missense_variant | Exon 2 of 12 | XP_024302432.1 | ||
ZP3 | NM_007155.6 | c.-67+6564C>G | intron_variant | Intron 1 of 8 | NP_009086.4 | |||
SSC4D | XM_017011750.2 | c.-33+5053G>C | intron_variant | Intron 1 of 7 | XP_016867239.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250080Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135184
GnomAD3 exomes
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1AN: 1461072Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726826
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
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31
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GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ExAC
AF:
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1
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
D
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of disorder (P = 0.0296);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at