rs141315088

Variant names:

• chr2-20204237-G-A
• rs141315088
• NM_002997.5:c.203C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002997.5(SDC1):​c.203C>T​(p.Thr68Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 1,593,916 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (4 hom., cov: 30)
  • Exomes 𝑓: 0.0032 (36 hom.)
• Consequence: SDC1 NM_002997.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.703
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026767552).
• BP6: Variant 2-20204237-G-A is Benign according to our data. Variant chr2-20204237-G-A is described in ClinVar as Benign. ClinVar VariationId is 790815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 454 AD gene.

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.203C>T	p.Thr68Met	missense	Exon 3 of 5	NP_002988.4
	SDC1	NM_001006946.2		c.203C>T	p.Thr68Met	missense	Exon 4 of 6	NP_001006947.2	P18827

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC1	ENST00000254351.9	TSL:1 MANE Select	c.203C>T	p.Thr68Met	missense	Exon 3 of 5	ENSP00000254351.4	P18827
	SDC1	ENST00000403076.5	TSL:1	c.203C>T	p.Thr68Met	missense	Exon 3 of 4	ENSP00000384613.1	E9PHH3
	SDC1	ENST00000381150.5	TSL:5	c.203C>T	p.Thr68Met	missense	Exon 4 of 6	ENSP00000370542.1	P18827

Frequencies

GnomAD3 genomes AF: 0.00309 AC: 454 AN: 147080 Hom.: 4 Cov.: 30

Gnomad AFR AF: 0.000636

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00704

Gnomad ASJ AF: 0.000307

Gnomad EAS AF: 0.00894

Gnomad SAS AF: 0.00986

Gnomad FIN AF: 0.00208

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00303

Gnomad OTH AF: 0.00649

GnomAD2 exomes AF: 0.00531 AC: 1266 AN: 238300 AF XY: 0.00542

Gnomad AFR exome AF: 0.000835

Gnomad AMR exome AF: 0.0106

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00706

Gnomad FIN exome AF: 0.00170

Gnomad NFE exome AF: 0.00333

Gnomad OTH exome AF: 0.00433

GnomAD4 exome AF: 0.00321 AC: 4643 AN: 1446716 Hom.: 36 Cov.: 38 AF XY: 0.00345 AC XY: 2487 AN XY: 720110

African (AFR) AF: 0.000717 AC: 24 AN: 33474

American (AMR) AF: 0.0123 AC: 548 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26114

East Asian (EAS) AF: 0.00408 AC: 162 AN: 39696

South Asian (SAS) AF: 0.0110 AC: 951 AN: 86236

European-Finnish (FIN) AF: 0.00290 AC: 112 AN: 38686

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5762

European-Non Finnish (NFE) AF: 0.00223 AC: 2474 AN: 1111778

Other (OTH) AF: 0.00594 AC: 358 AN: 60296

GnomAD4 genome AF: 0.00308 AC: 454 AN: 147200 Hom.: 4 Cov.: 30 AF XY: 0.00296 AC XY: 213 AN XY: 71920

African (AFR) AF: 0.000634 AC: 26 AN: 41010

American (AMR) AF: 0.00703 AC: 103 AN: 14646

Ashkenazi Jewish (ASJ) AF: 0.000307 AC: 1 AN: 3260

East Asian (EAS) AF: 0.00896 AC: 46 AN: 5136

South Asian (SAS) AF: 0.00966 AC: 46 AN: 4762

European-Finnish (FIN) AF: 0.00208 AC: 21 AN: 10100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00303 AC: 197 AN: 65092

Other (OTH) AF: 0.00691 AC: 14 AN: 2026

Alfa AF: 0.00313 Hom.: 9

Bravo AF: 0.00338

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00279 AC: 24

ExAC AF: 0.00544 AC: 659

Asia WGS AF: 0.0140 AC: 48 AN: 3478

EpiCase AF: 0.00185

EpiControl AF: 0.00190

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.11
DANN	Benign	0.53
DEOGEN2	Benign	0.37	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0035	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.64	N
PhyloP100		-0.70
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.034
Sift	Benign	0.45	T
Sift4G	Benign	0.19	T
Polyphen		0.0070	B
Vest4		0.037
MVP		0.072
MPC		0.25
ClinPred		0.0097	T
GERP RS		-9.0
Varity_R		0.0098
gMVP		0.063
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs141315088; hg19: chr2-20403998; COSMIC: COSV105031658;