Genetic Variant SDC1:p.Thr122Ser (chr2-20204075-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002997.5(SDC1):c.365C>G(p.Thr122Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. T122N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SDC1
NM_002997.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.77

Publications

1 publications found

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]

SDC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14457726).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002997.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC1	NM_002997.5	MANE Select	c.365C>G	p.Thr122Ser	missense	Exon 3 of 5	NP_002988.4
	SDC1	NM_001006946.2		c.365C>G	p.Thr122Ser	missense	Exon 4 of 6	NP_001006947.2	P18827

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SDC1	ENST00000254351.9	TSL:1 MANE Select	c.365C>G	p.Thr122Ser	missense	Exon 3 of 5	ENSP00000254351.4	P18827
SDC1	ENST00000403076.5	TSL:1	c.365C>G	p.Thr122Ser	missense	Exon 3 of 4	ENSP00000384613.1	E9PHH3
SDC1	ENST00000381150.5	TSL:5	c.365C>G	p.Thr122Ser	missense	Exon 4 of 6	ENSP00000370542.1	P18827

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458888

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725882

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111894

Other (OTH)

AF:

0.00

AC:

AN:

60366

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.42

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.27

M_CAP

Benign

0.0043

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

PhyloP100

1.8

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.7

REVEL

Benign

0.043

Sift

Benign

0.061

Sift4G

Uncertain

0.0090

Polyphen

0.0050

Vest4

0.048

MutPred

0.44

Loss of glycosylation at T122 (P = 0.0814)

MVP

0.69

MPC

0.22

ClinPred

0.11

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.039

gMVP

0.12

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over