Genetic Variant NM_018074.6:c.633C>T (chr19-4262039-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018074.6(YJU2):c.633C>T(p.Ser211Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00565 in 1,613,122 control chromosomes in the GnomAD database, including 449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 222 hom., cov: 31)

Exomes 𝑓: 0.0032 ( 227 hom. )

Consequence

YJU2
NM_018074.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -7.21

Publications

1 publications found

Variant links:

Genes affected

YJU2 (HGNC:25518): (YJU2 splicing factor homolog) Predicted to enable metal ion binding activity. Predicted to be involved in RNA splicing and negative regulation of DNA damage response, signal transduction by p53 class mediator. Part of U2-type catalytic step 1 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

YJU2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 19-4262039-C-T is Benign according to our data. Variant chr19-4262039-C-T is described in ClinVar as Benign. ClinVar VariationId is 785913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-7.21 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0991 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018074.6. 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
	YJU2	NM_018074.6	MANE Select	c.633C>T	p.Ser211Ser	synonymous	Exon 6 of 8	NP_060544.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YJU2	ENST00000262962.12	TSL:1 MANE Select	c.633C>T	p.Ser211Ser	synonymous	Exon 6 of 8	ENSP00000262962.6	Q9BW85
	YJU2	ENST00000872338.1		c.633C>T	p.Ser211Ser	synonymous	Exon 6 of 8	ENSP00000542397.1

Frequencies

GnomAD3 genomes

AF:

0.0292

AC:

4437

AN:

152028

Hom.:

219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0117

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0201

GnomAD2 exomes

AF:

0.00768

AC:

1921

AN:

250234

AF XY:

0.00571

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.00515

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.00311

GnomAD4 exome

AF:

0.00318

AC:

4644

AN:

1460976

Hom.:

227

Cov.:

AF XY:

0.00276

AC XY:

2006

AN XY:

726832

show subpopulations

African (AFR)

AF:

0.108

AC:

3628

AN:

33460

American (AMR)

AF:

0.00573

AC:

256

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000301

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52672

Middle Eastern (MID)

AF:

0.00451

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000268

AC:

298

AN:

1111910

Other (OTH)

AF:

0.00674

AC:

407

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

199

398

598

797

996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

224

336

448

560

<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:

0.0293

AC:

4465

AN:

152146

Hom.:

222

Cov.:

AF XY:

0.0284

AC XY:

2115

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.102

AC:

4218

AN:

41506

American (AMR)

AF:

0.0117

AC:

178

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

67986

Other (OTH)

AF:

0.0199

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

192

385

577

770

962

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0121

Hom.:

Bravo

AF:

0.0338

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000356

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

-0.53

CADD

Benign

0.016

(source)

DANN

Benign

0.79

PhyloP100

-7.2

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over