rs2230924

Variant summary

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

The NM_002997.5(SDC1):​c.252G>T​(p.Glu84Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,904 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 30)

Consequence

SDC1
NM_002997.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.65
Variant links:
Genes affected
SDC1 (HGNC:10658): (syndecan 1) The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein. The syndecan-1 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Altered syndecan-1 expression has been detected in several different tumor types. While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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=0.04283029).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SDC1NM_002997.5 linkuse as main transcriptc.252G>T p.Glu84Asp missense_variant 3/5 ENST00000254351.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SDC1ENST00000254351.9 linkuse as main transcriptc.252G>T p.Glu84Asp missense_variant 3/51 NM_002997.5 P1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151904
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000945
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
45
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151904
Hom.:
0
Cov.:
30
AF XY:
0.0000135
AC XY:
1
AN XY:
74166
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000945
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
0.0010
DANN
Benign
0.55
DEOGEN2
Benign
0.29
T;T;.;.
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.0031
N
LIST_S2
Benign
0.53
.;T;T;T
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.043
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-1.2
N;N;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.50
N;N;N;N
REVEL
Benign
0.031
Sift
Benign
1.0
T;T;T;T
Sift4G
Benign
0.64
T;T;T;.
Polyphen
0.0
B;B;B;.
Vest4
0.028
MutPred
0.23
Loss of glycosylation at P80 (P = 0.1663);Loss of glycosylation at P80 (P = 0.1663);Loss of glycosylation at P80 (P = 0.1663);.;
MVP
0.34
MPC
0.21
ClinPred
0.062
T
GERP RS
-7.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.033
gMVP
0.038

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs2230924; hg19: chr2-20403949; API