Genetic Variant NM_014654.4:c.*166C>T (chr1-30873045-G-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.*166C>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 0.0869 in 643,326 control chromosomes in the GnomAD database, including 2,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 678 hom., cov: 32)

Exomes 𝑓: 0.085 ( 1933 hom. )

Consequence

SDC3
NM_014654.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.09

Publications

5 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=-0.87).

BP6

Variant 1-30873045-G-A is Benign according to our data. Variant chr1-30873045-G-A is described in ClinVar as Benign. ClinVar VariationId is 1289937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 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.*166C>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.*166C>T	3_prime_UTR	Exon 5 of 5	ENSP00000344468.6	O75056
SDC3	ENST00000336798.11	TSL:1	c.*166C>T	3_prime_UTR	Exon 3 of 3	ENSP00000338346.7	A0A9K3Y886
SDC3	ENST00000937355.1		c.*166C>T	3_prime_UTR	Exon 5 of 5	ENSP00000607414.1

Frequencies

GnomAD3 genomes

AF:

0.0922

AC:

14020

AN:

152132

Hom.:

677

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.0396

Gnomad AMR

AF:

0.0606

Gnomad ASJ

AF:

0.0873

Gnomad EAS

AF:

0.0383

Gnomad SAS

AF:

0.0590

Gnomad FIN

AF:

0.0829

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0927

Gnomad OTH

AF:

0.0891

GnomAD4 exome

AF:

0.0853

AC:

41872

AN:

491076

Hom.:

1933

Cov.:

AF XY:

0.0846

AC XY:

22103

AN XY:

261290

show subpopulations

African (AFR)

AF:

0.120

AC:

1648

AN:

13720

American (AMR)

AF:

0.0487

AC:

1056

AN:

21668

Ashkenazi Jewish (ASJ)

AF:

0.0901

AC:

1266

AN:

14048

East Asian (EAS)

AF:

0.0357

AC:

1189

AN:

33314

South Asian (SAS)

AF:

0.0570

AC:

2828

AN:

49624

European-Finnish (FIN)

AF:

0.0946

AC:

3671

AN:

38788

Middle Eastern (MID)

AF:

0.0884

AC:

179

AN:

2024

European-Non Finnish (NFE)

AF:

0.0949

AC:

27548

AN:

290384

Other (OTH)

AF:

0.0904

AC:

2487

AN:

27506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1874

3748

5622

7496

9370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

170

340

510

680

850

<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:

0.0922

AC:

14031

AN:

152250

Hom.:

678

Cov.:

AF XY:

0.0888

AC XY:

6609

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.118

AC:

4889

AN:

41544

American (AMR)

AF:

0.0604

AC:

924

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0873

AC:

303

AN:

3472

East Asian (EAS)

AF:

0.0388

AC:

201

AN:

5184

South Asian (SAS)

AF:

0.0587

AC:

283

AN:

4824

European-Finnish (FIN)

AF:

0.0829

AC:

880

AN:

10620

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0926

AC:

6299

AN:

67996

Other (OTH)

AF:

0.0882

AC:

186

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

676

1352

2029

2705

3381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

320

480

640

800

<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:

0.0893

Hom.:

878

Bravo

AF:

0.0908

Asia WGS

AF:

0.0750

AC:

260

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

-0.87

CADD

Benign

0.44

(source)

DANN

Benign

0.47

PhyloP100

-2.1

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