rs4949184

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000339394.7(SDC3):​c.907G>T​(p.Asp303Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000342 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D303N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

SDC3
ENST00000339394.7 missense

Scores

1
7
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.46
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.3983986).
BS2
High AC in GnomAdExome4 at 50 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SDC3NM_014654.4 linkuse as main transcriptc.907G>T p.Asp303Tyr missense_variant 4/5 ENST00000339394.7 NP_055469.3
SDC3XM_011542463.1 linkuse as main transcriptc.874G>T p.Asp292Tyr missense_variant 4/5 XP_011540765.1
SDC3XM_011542464.3 linkuse as main transcriptc.871G>T p.Asp291Tyr missense_variant 4/5 XP_011540766.1
SDC3XM_011542466.2 linkuse as main transcriptc.781G>T p.Asp261Tyr missense_variant 4/5 XP_011540768.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SDC3ENST00000339394.7 linkuse as main transcriptc.907G>T p.Asp303Tyr missense_variant 4/51 NM_014654.4 ENSP00000344468 P1
SDC3ENST00000336798.11 linkuse as main transcriptc.733G>T p.Asp245Tyr missense_variant 2/31 ENSP00000338346

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251266
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135802
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000342
AC:
50
AN:
1461834
Hom.:
0
Cov.:
35
AF XY:
0.0000248
AC XY:
18
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.0000441
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.43
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.72
.;D
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.76
T;T
M_CAP
Benign
0.0064
T
MetaRNN
Benign
0.40
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
.;L
MutationTaster
Benign
0.98
P;P
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-3.3
D;D
REVEL
Benign
0.047
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.024
D;D
Polyphen
0.82
P;P
Vest4
0.55
MutPred
0.32
.;Gain of catalytic residue at L298 (P = 0.048);
MVP
0.11
MPC
0.082
ClinPred
0.93
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.27
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs4949184; hg19: chr1-31347399; API