rs2282440
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_014654.4(SDC3):c.986C>T(p.Thr329Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0352 in 1,614,092 control chromosomes in the GnomAD database, including 9,101 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).
Frequency
Genomes: 𝑓 0.047 ( 984 hom., cov: 32)
Exomes 𝑓: 0.034 ( 8117 hom. )
Consequence
SDC3
NM_014654.4 missense
NM_014654.4 missense
Scores
2
14
Clinical Significance
Conservation
PhyloP100: 2.79
Genes affected
SDC3 (HGNC:10660): (syndecan 3) The protein encoded by this gene belongs to the syndecan proteoglycan family. It may play a role in the organization of cell shape by affecting the actin cytoskeleton, possibly by transferring signals from the cell surface in a sugar-dependent mechanism. Allelic variants of this gene have been associated with obesity. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=3.3020973E-4).
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SDC3 | NM_014654.4 | c.986C>T | p.Thr329Ile | missense_variant | 4/5 | ENST00000339394.7 | |
SDC3 | XM_011542463.1 | c.953C>T | p.Thr318Ile | missense_variant | 4/5 | ||
SDC3 | XM_011542464.3 | c.950C>T | p.Thr317Ile | missense_variant | 4/5 | ||
SDC3 | XM_011542466.2 | c.860C>T | p.Thr287Ile | missense_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SDC3 | ENST00000339394.7 | c.986C>T | p.Thr329Ile | missense_variant | 4/5 | 1 | NM_014654.4 | P1 | |
SDC3 | ENST00000336798.11 | c.812C>T | p.Thr271Ile | missense_variant | 2/3 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0474 AC: 7203AN: 152118Hom.: 974 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0927 AC: 23307AN: 251464Hom.: 3783 AF XY: 0.0856 AC XY: 11629AN XY: 135908
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GnomAD4 exome AF: 0.0340 AC: 49660AN: 1461856Hom.: 8117 Cov.: 33 AF XY: 0.0349 AC XY: 25396AN XY: 727242
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GnomAD4 genome ? AF: 0.0475 AC: 7225AN: 152236Hom.: 984 Cov.: 32 AF XY: 0.0564 AC XY: 4195AN XY: 74412
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ESP6500AA
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ExAC
?
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10416
Asia WGS
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883
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ClinVar
Significance: association
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Obesity, association with Other:1
association, no assertion criteria provided | literature only | OMIM | May 01, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
P;P
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MPC
0.072
ClinPred
T
GERP RS
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