dbSNP rs7850023: UGCG:p.Thr287Thr (chr9-111932206-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003358.3(UGCG):c.861A>G(p.Thr287Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,613,606 control chromosomes in the GnomAD database, including 64,130 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 7576 hom., cov: 32)

Exomes 𝑓: 0.27 ( 56554 hom. )

Consequence

UGCG
NM_003358.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.339

Publications

18 publications found

Variant links:

Genes affected

UGCG (HGNC:12524): (UDP-glucose ceramide glucosyltransferase) This gene encodes an enzyme that catalyzes the first glycosylation step in the biosynthesis of glycosphingolipids, which are membrane components containing lipid and sugar moieties. The product of this reaction is glucosylceramide, which is the core structure of many glycosphingolipids. [provided by RefSeq, Dec 2014]

UGCG links:

MIR4668 (HGNC:41545): (microRNA 4668) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR4668 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP7

Synonymous conserved (PhyloP=0.339 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGCG	NM_003358.3 link	c.861A>G	p.Thr287Thr	synonymous_variant	Exon 8 of 9	ENST00000374279.4	NP_003349.1	Q16739A0A024R157

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGCG	ENST00000374279.4 link	c.861A>G	p.Thr287Thr	synonymous_variant	Exon 8 of 9	1	NM_003358.3	ENSP00000363397.3		Q16739
MIR4668	ENST00000582284.1 link	n.*37A>G		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46862

AN:

151858

Hom.:

7565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.356

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.266

Gnomad FIN

AF:

0.328

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.287

GnomAD2 exomes

AF:

0.308

AC:

77356

AN:

251300

AF XY:

0.298

show subpopulations

Gnomad AFR exome

AF:

0.358

Gnomad AMR exome

AF:

0.482

Gnomad ASJ exome

AF:

0.220

Gnomad EAS exome

AF:

0.274

Gnomad FIN exome

AF:

0.315

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.294

GnomAD4 exome

AF:

0.274

AC:

400919

AN:

1461630

Hom.:

56554

Cov.:

AF XY:

0.273

AC XY:

198477

AN XY:

727146

show subpopulations

African (AFR)

AF:

0.360

AC:

12058

AN:

33472

American (AMR)

AF:

0.467

AC:

20900

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

5826

AN:

26134

East Asian (EAS)

AF:

0.236

AC:

9365

AN:

39694

South Asian (SAS)

AF:

0.269

AC:

23239

AN:

86240

European-Finnish (FIN)

AF:

0.316

AC:

16890

AN:

53418

Middle Eastern (MID)

AF:

0.255

AC:

1472

AN:

5768

European-Non Finnish (NFE)

AF:

0.265

AC:

294749

AN:

1111798

Other (OTH)

AF:

0.272

AC:

16420

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

15492

30984

46477

61969

77461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10038

20076

30114

40152

50190

<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:

0.309

AC:

46926

AN:

151976

Hom.:

7576

Cov.:

AF XY:

0.313

AC XY:

23274

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.357

AC:

14772

AN:

41434

American (AMR)

AF:

0.401

AC:

6119

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

802

AN:

3468

East Asian (EAS)

AF:

0.274

AC:

1417

AN:

5178

South Asian (SAS)

AF:

0.267

AC:

1284

AN:

4814

European-Finnish (FIN)

AF:

0.328

AC:

3467

AN:

10556

Middle Eastern (MID)

AF:

0.305

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.267

AC:

18138

AN:

67944

Other (OTH)

AF:

0.286

AC:

604

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1628

3257

4885

6514

8142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<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:

0.285

Hom.:

11745

Bravo

AF:

0.317

Asia WGS

AF:

0.277

AC:

961

AN:

3478

EpiCase

AF:

0.260

EpiControl

AF:

0.260

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.0

(source)

DANN

Benign

0.69

PhyloP100

0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over