Genetic Variant SDC3:c.*273A>T (chr1-30872938-T-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014654.4(SDC3):c.*273A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0745 in 441,146 control chromosomes in the GnomAD database, including 1,445 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 396 hom., cov: 32)

Exomes 𝑓: 0.079 ( 1049 hom. )

Consequence

SDC3
NM_014654.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.358

Publications

4 publications found

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]

SDC3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-30872938-T-A is Benign according to our data. Variant chr1-30872938-T-A is described in ClinVar as Benign. ClinVar VariationId is 1287484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014654.4. 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
	SDC3	NM_014654.4	MANE Select	c.*273A>T		3_prime_UTR	Exon 5 of 5	NP_055469.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SDC3	ENST00000339394.7	TSL:1 MANE Select	c.*273A>T	3_prime_UTR	Exon 5 of 5	ENSP00000344468.6	O75056
SDC3	ENST00000336798.11	TSL:1	c.*273A>T	3_prime_UTR	Exon 3 of 3	ENSP00000338346.7	A0A9K3Y886
SDC3	ENST00000937355.1		c.*273A>T	3_prime_UTR	Exon 5 of 5	ENSP00000607414.1

Frequencies

GnomAD3 genomes

AF:

0.0652

AC:

9913

AN:

152074

Hom.:

396

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0256

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0502

Gnomad ASJ

AF:

0.0691

Gnomad EAS

AF:

0.0382

Gnomad SAS

AF:

0.0589

Gnomad FIN

AF:

0.0825

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0922

Gnomad OTH

AF:

0.0712

GnomAD4 exome

AF:

0.0794

AC:

22941

AN:

288954

Hom.:

1049

Cov.:

AF XY:

0.0793

AC XY:

11761

AN XY:

148384

show subpopulations

African (AFR)

AF:

0.0229

AC:

215

AN:

9382

American (AMR)

AF:

0.0464

AC:

470

AN:

10124

Ashkenazi Jewish (ASJ)

AF:

0.0724

AC:

704

AN:

9724

East Asian (EAS)

AF:

0.0348

AC:

758

AN:

21756

South Asian (SAS)

AF:

0.0523

AC:

952

AN:

18220

European-Finnish (FIN)

AF:

0.0926

AC:

1835

AN:

19818

Middle Eastern (MID)

AF:

0.0810

AC:

110

AN:

1358

European-Non Finnish (NFE)

AF:

0.0913

AC:

16504

AN:

180698

Other (OTH)

AF:

0.0779

AC:

1393

AN:

17874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

994

1987

2981

3974

4968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

258

344

430

<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

AF:

0.0651

AC:

9913

AN:

152192

Hom.:

396

Cov.:

AF XY:

0.0633

AC XY:

4708

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0256

AC:

1063

AN:

41530

American (AMR)

AF:

0.0502

AC:

767

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0691

AC:

240

AN:

3472

East Asian (EAS)

AF:

0.0387

AC:

200

AN:

5174

South Asian (SAS)

AF:

0.0587

AC:

283

AN:

4818

European-Finnish (FIN)

AF:

0.0825

AC:

874

AN:

10598

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0922

AC:

6270

AN:

67984

Other (OTH)

AF:

0.0704

AC:

149

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

479

958

1438

1917

2396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0888

Hom.:

Bravo

AF:

0.0596

Asia WGS

AF:

0.0700

AC:

245

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.1

(source)

DANN

Benign

0.73

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over