chr14-69952282-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001034852.3(SMOC1):c.244G>A(p.Val82Met) variant causes a missense change. The variant allele was found at a frequency of 0.00096 in 1,614,176 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: 𝑓 0.0046 ( 4 hom., cov: 33)
Exomes 𝑓: 0.00058 ( 3 hom. )
Consequence
SMOC1
NM_001034852.3 missense
NM_001034852.3 missense
Scores
6
11
Clinical Significance
Conservation
PhyloP100: 3.75
Genes affected
SMOC1 (HGNC:20318): (SPARC related modular calcium binding 1) This gene encodes a multi-domain secreted protein that may have a critical role in ocular and limb development. Mutations in this gene are associated with microphthalmia and limb anomalies. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008308232).
BP6
?
Variant 14-69952282-G-A is Benign according to our data. Variant chr14-69952282-G-A is described in ClinVar as [Benign]. Clinvar id is 789814.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-69952282-G-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0046 (701/152310) while in subpopulation AFR AF= 0.0155 (643/41564). AF 95% confidence interval is 0.0145. There are 4 homozygotes in gnomad4. There are 334 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMOC1 | NM_001034852.3 | c.244G>A | p.Val82Met | missense_variant | 2/12 | ENST00000361956.8 | |
SMOC1 | NM_022137.6 | c.244G>A | p.Val82Met | missense_variant | 2/12 | ||
SMOC1 | XM_005267995.2 | c.244G>A | p.Val82Met | missense_variant | 2/12 | ||
SMOC1 | XM_005267996.2 | c.244G>A | p.Val82Met | missense_variant | 2/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMOC1 | ENST00000361956.8 | c.244G>A | p.Val82Met | missense_variant | 2/12 | 1 | NM_001034852.3 | A2 | |
SMOC1 | ENST00000381280.4 | c.244G>A | p.Val82Met | missense_variant | 2/12 | 1 | P4 | ||
SMOC1 | ENST00000553839.1 | n.146G>A | non_coding_transcript_exon_variant | 1/4 | 5 | ||||
SMOC1 | ENST00000555917.1 | n.549G>A | non_coding_transcript_exon_variant | 4/4 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00460 AC: 700AN: 152192Hom.: 4 Cov.: 33
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GnomAD3 exomes AF: 0.00123 AC: 310AN: 251292Hom.: 3 AF XY: 0.000957 AC XY: 130AN XY: 135804
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GnomAD4 exome AF: 0.000580 AC: 848AN: 1461866Hom.: 3 Cov.: 33 AF XY: 0.000505 AC XY: 367AN XY: 727240
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;D
Vest4
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